Open Access

Haemophilus parasuis: infection, immunity and enrofloxacin

Veterinary Research201546:128

DOI: 10.1186/s13567-015-0263-3

Received: 27 February 2015

Accepted: 2 October 2015

Published: 28 October 2015

Abstract

Haemophilus parasuis is an early colonizer of the porcine upper respiratory tract and is the etiological agent of Glasser’s disease. The factors responsible for H. parasuis colonization and systemic infection are not yet well understood, while prevention and control of Glasser’s disease continues to be challenging. Recent studies on innate immunity to H. parasuis have demonstrated that porcine alveolar macrophages (PAMs) are able to differentially up-regulate several genes related to inflammation and phagocytosis, and several pro-inflammatory cytokines are produced by porcine cells upon exposure to H. parasuis. The susceptibility of H. parasuis strains to phagocytosis by PAMs and the bactericidal effect of complement are influenced by the virulent phenotype of the strains. While non-virulent strains are susceptible to phagocytosis and complement, virulent strains are resistant to both. However, in the presence of specific antibodies against H. parasuis, virulent strains become susceptible to phagocytosis. More information is still needed, though, in order to better understand the host immune responses to H. parasuis. Antimicrobials are commonly used in the swine industry to help treat and control Glasser’s disease. Some of the common antimicrobials have been shown to reduce colonization by H. parasuis, which may have implications for disease dynamics, development of effective immune responses and immunomodulation. Here, we provide the current state of research on innate and adaptive immune responses to H. parasuis and discuss the potential effect of enrofloxacin on the development of a protective immune response against H. parasuis infection.

1 Table of Contents

1 Introduction

2 Protective immunity against H. parasuis

2.1 Innate defense mechanisms to H. parasuis

2.2 Acquired defense mechanisms against H. parasuis

3 Effects of enrofloxacin on the immune response

4 Conclusions

2 Introduction

Haemophilus parasuis is one of the most important bacteria affecting pigs. The disease caused by this pathogen is characterized by polyserositis and it is known as Glasser’s disease [1]. H. parasuis is present in all major swine-rearing countries and remains a significant pathogen in contemporary swine production systems [1]. In addition to causing disease, H. parasuis is frequently isolated from the upper respiratory tract of healthy pigs [2, 3]. Multiple different genotypes and serotypes of H. parasuis have been described. However, there is not a clear association between virulence and H. parasuis phenotypes or genotypes [4]. Successful vaccination resulting in decreased mortality has been achieved by bacterins and autogenous vaccines, but failures are frequent due to poor cross-protection [58]. The ability of H. parasuis to interact with the swine host, causing or not disease, is a subject that needs further investigation. Recently, reverse vaccinology and immunoproteomic analysis identified several putative virulence-associated genes and immunogenic proteins in different H. parasuis strains [912]. Follow-up vaccine studies in mice and piglets using recombinant antigens revealed strong seroconversion, but only partial protection against homologous challenge and weak or inexistent cross-protection [13, 14].

Because of the incomplete efficacy of vaccines, antimicrobials are needed to treat H. parasuis infections [1]. Pigs receiving antimicrobials early during infection with H. parasuis are usually able to survive a systemic infection [1]. More specifically, enrofloxacin is a fluoroquinolone active against Gram-negative and Gram-positive bacteria [15]. Enrofloxacin inhibits the bacterial DNA gyrase (a type II topoisomerase), preventing DNA supercoiling and replication, which leads to cell death [16]. Additionally, enrofloxacin has been shown to temporarily decrease the load of H. parasuis naturally colonizing the upper respiratory tract of conventional pigs [3].

Even though there is not a standard method for evaluating the antimicrobial susceptibility against H. parasuis [17], some studies that included Spanish [18] and Chinese [19] strains have shown antimicrobial resistance to enrofloxacin using breakpoints recommended by the Clinical and Laboratory Standard Institute (CLSI) for other bacterial species. Although many H. parasuis strains are considered susceptible to enrofloxacin, it is important to emphasize the judicious use of antimicrobials to treat Glasser’s disease and to monitor susceptibility patterns of H. parasuis isolates before administration of a given therapy.

Enrofloxacin has also been shown to hinder immunity to several bacterial species, including Actinobacillus pleuropneumoniae in swine [20]. Moreover, early elimination of various bacterial pathogens by antimicrobials hindered the development of protective immune responses necessary to overcome future infections [2123]. While it is clear that the use of antimicrobials exert a direct deleterious effect over bacterial infections, recent findings described below are shedding light on their potential effect on immune responses. However, the interaction between antimicrobials and immune responses to H. parasuis is not known. The purpose of the present review is to summarize existing knowledge concerning the swine immune response to H. parasuis and we discuss the potential mechanisms for interaction between enrofloxacin and immunity.

3 Protective immunity against H. parasuis

There has been a great expansion on knowledge in regards to the pig immune system and its effect in disease and protective immunity against infections. Pigs can respond almost immediately to an infectious agent through innate immune mechanisms, which might control the infection until activation of the adaptive immune system [23]. Shortly after infection, bacteria encounters the innate immune system, which is activated when pattern-recognition receptors (PRRs), including toll-like receptors (TLRs), contact pathogen-associated molecular patterns (PAMPs) and induce different signaling pathways [24]. Bacterial invasion also triggers the complement system [25], induces migration of phagocytic cells and the production of various cytokines, which provides antimicrobial defense, recruit of more cells through the inflammatory process and assists in the activation of acquired immunity [23].

The activation of the acquired immune response results in additional cytokine production, T-cell and B-cell activation, and antibody production. The acquired immune response also provides the host with specific memory for protection against subsequent homologous infections [23]. Specific reagents, improved technology and more detailed knowledge of the porcine immune cell populations now enable detailed analyses of the antigen-specific immune responses in swine [2629]. Although protective immunity against extracellular bacteria is largely dependent on antibodies, cellular responses are often required for full expression of immunity [23].

3.1 Innate defense mechanisms to H. parasuis

Porcine alveolar macrophages (PAMs) are considered an important line of defense against H. parasuis infection [30]. PAMs isolated from pigs inoculated with H. parasuis were able to differentially up-regulate several genes related to cytokine production, phagocytosis, formation of phagolysosome, signal transduction and nitric oxide production [31].

In vitro studies have demonstrated that non-virulent strains are susceptible to phagocytosis by PAMs, while virulent H. parasuis strains are resistant [30]. Differently from the mechanism of phagocytosis for non-virulent strains, phagocytosis of virulent strains is not dependent on actin filaments [30]. In addition, competition assays have shown that phagocytosis of H. parasuis is probably not dependent on a specific receptor, since phagocytosis of non-virulent strains was not affected by the presence of non-virulent or virulent strains [30].

Moreover, in vivo studies have shown that there is a delay in the processing of virulent H. parasuis strains by PAMs and a 24 h delay in macrophage activation by H. parasuis virulent strains when compared to non-virulent strains [32]. While there is no difference on association of virulent and non-virulent strains with early endosomes, non-virulent strains were found more frequently associated with mature endosomes than virulent strains after one-hour incubation [33]. This inhibition of early host responses to virulent H. parasuis may lead to the development of Glasser’s disease [32]. Interference of phagocytosis by H. parasuis virulent strains is likely associated with presence of capsule [30]. Additionally, two virulent-associated trimeric autotransporter (VtaA) antigens, VtaA 8 and VtaA 9, identified in the H. parasuis outer membrane, delayed interactions with macrophages, even though they did not prevent phagocytosis [33].

Immunohistochemistry and immunoperoxidase techniques have also demonstrated that following systemic infection, H. parasuis antigens were found as degenerated bacteria in dilated phagosomes in serosal lesions [34, 35]. Apparently, late leukocyte responses that are activated after infection with virulent strains are able to efficiently phagocytize H. parasuis, which is in agreement with in vitro studies that have shown that virulent H. parasuis strains do not survive inside macrophages when internalized [30].

Cytokines participating in the inflammatory response to H. parasuis including interleukin (IL)-8 and IL-6, were produced by porcine tracheal and endothelial cells upon contact with H. parasuis [36, 37]. Acute phase response stimulated by IL-6 production and chemoattraction of leukocytes stimulated by IL-8 represent essential roles of these cytokines in inflammatory response to H. parasuis [36]. Furthermore, increased IL-1α expression in lung has been reported in pigs undergoing severe Glasser’s disease following experimental infection, whereas IL-4, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were expressed in significantly higher levels in spleen, pharyngeal lymph nodes, lung and brain of survivors [38]. Similarly, in vivo studies with pigs challenged with highly virulent H. parasuis showed an increase proportion of CD163+ monocytes, which are able to produce high amounts of proinflammatory cytokines, such as TNF-α, IL-1 and IL-6 [39].

As part of another line of defense of the innate immune response, γδ T-cells were found in reduced numbers in pigs after challenge with a lethal dose of a highly virulent H. parasuis strain [39]. γδ T-cells represent a numerous lymphocyte subset population in pigs able to recognize unprocessed non-peptide antigens [26]. These cells can cause cytotoxicity and produce T helper (Th)-1 and Th-2 cytokines that contribute to inflammatory and anti-inflammatory immune response [31]. A reduction on γδ T-cells might render the pigs more susceptible to H. parasuis infection, suggesting that this could be one of the mechanisms of pathogenesis of H. parasuis virulent strains even though such mechanism still needs to be elucidated [39].

Antibody-independent activation of the complement cascade is an initial host’s defense mechanism, causing vasodilatation and increased vascular permeability resulting in attraction of phagocytic cells to the site of infection [23]. The complement cascade also results in the formation of a complex of proteins that acts as a pore in the bacterial wall ultimately causing bacterial lysis. The activation of complement can be made by bacterial endotoxins such as lipopolysaccharides (LPS), peptidoglycan and teichoic acids [23]. Non-virulent H. parasuis strains were susceptible to complement in an antibody-independent way, while virulent strains evade this host response and resist to complement-mediated killing [40]. Therefore, resistance to antibody-independent complement killing seems to be a mechanism of pathogenicity of H. parasuis virulent strains [40] and it was demonstrated that the H. parasuis outer membrane protein P2 (OmpP2) is required for serum resistance [41].

3.2 Acquired defense mechanisms against H. parasuis

While the porcine innate immune system confers initial protection, the acquired immune system provides a second, more specific and long lasting, line of defense against infectious organisms [25]. According to studies performed in mice, following antigen stimulation, Th cells differentiate into Th-1 or Th-2 cells. The functions of Th-1 and Th-2 cells correlate with the production of their cytokines. Th-1 cells are involved in cell-mediated inflammatory functions through secretion of IL-2 and IFN-γ. Th-2 cells encourage antibody production, and also enhance eosinophil proliferation and function by secreting IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13 [42]. Accordingly, Th-2 cytokines are commonly found in association with antibody responses [42], even though in pigs the Th-2 cytokine, IL-4, was not able to stimulate porcine B-cell and antibody production in vitro [43].

Significant rises in the total proportion of Th-1 and Th-2 (CD4+) cells were observed in all pigs that survived challenge with live H. parasuis, while susceptible pigs showed a decrease of CD4+ T cells [44]. Cytotoxic (CD8+) T cells and B-cells were significantly increased in all pigs between 1 and 3 days after challenge, independently of survival [39]. Further studies are needed to elucidate cellular immune responses to H. parasuis infection that are related to protection.

A humoral immune response is usually activated when pigs are infected with H. parasuis [35]. Such response is frequently associated with the development of a transient IgM response followed by a solid and progressively increasing IgG antibody response [45]. Moreover, passive immunization of pigs with serum containing specific antibodies against H. parasuis confirmed the role of the humoral response on protection against lethal challenge [46]. The mechanism of protection by antibodies seems to be due to the role of antibodies in opsonization of H. parasuis strains to facilitate phagocytosis [30]. In particular, virulent H. parasuis strains require prior opsonization with specific antibodies in order to be phagocytosed by PAMs and, if internalized, they are successfully killed by PAMs [30].

In comparison with the amount of information available on the immune response to H. parasuis systemic infection, knowledge on immune response to H. parasuis colonization is limited, even though H. parasuis is a common colonizer of pigs. It has been demonstrated that non-virulent H. parasuis strains possess mechanisms of immune evasion, such as biofilm formation [47]. Biofilm formation might protect bacteria from the attack of the host immune response and facilitate colonization of the upper respiratory tract by non-virulent strains. In addition, non-virulent strains are usually susceptible to phagocytosis by PAMs [30] and sensitive to the bactericidal effects of serum [48], which might prevent bacteria from surviving in the lungs and invading systemically the hosts. In addition, an increase in H. parasuis colonization rate was associated with a decrease in H. parasuis serum antibodies [2]. Therefore, serum antibodies in piglets might be able to modulate the timing and level of colonization by H. parasuis, and be relevant to avoid systemic disease caused by H. parasuis [2].

4 Effects of enrofloxacin on the immune response

Most of the findings reporting the interactions of antimicrobials with the immune system were discovered using mouse models [21, 22]. These findings contribute to the understanding of how the use of antimicrobial drugs can interfere with protection against a specific bacterial infection, either by interacting with the cellular and/or humoral immune response or by decreasing the antigen responsible for triggering an immune response. However, the mechanisms by which they act still need to be further investigated, especially for large animals.

Enrofloxacin, a fluoroquinolone, is actively accumulated in phagocytes, but it did not interfere with the chemotaxic action of porcine polymorphonuclear leukocytes (PMNs) or phagocytosis of A. pleuropneumoniae, Pasteurella multocida and Staphylococcus aureus by PMNs and PAMs when compared to untreated controls [49]. However, the intraphagocytic killing of A. pleuropneumoniae was significantly enhanced by enrofloxacin in both PMNs and PAMs [49]. More research is needed, though, to investigate whether these effects would also apply to H. parasuis.

In swine, a protective humoral immune response to A. pleuropneumoniae was impeded by treatment with enrofloxacin but not by treatment with penicillin or tetracycline [20]. Absence of seroconversion might have been related to the high efficiency of enrofloxacin in eliminating the inoculated A. pleuropneumoniae quickly enough to prevent the activation of an acquired immune response. Regarding H. parasuis, even though there is no specific information available on antimicrobial interference on the immune response, it is known that enrofloxacin is able to reduce the load of H. parasuis in the upper respiratory tract of naturally colonized pigs [3]. Interference with H. parasuis colonization might be associated with interference with the development of a protective immune response to colonizing bacteria, since pigs experimentally inoculated with a low dose of virulent H. parasuis strain were less susceptible to Glasser’s disease in the field [50, 51].

5 Conclusions

Protection against H. parasuis disease involves the activation of several elements of the innate and acquired porcine immune system, most of which are still unknown. Specific H. parasuis virulent factors allow this bacterium to evade the innate immune system and invade systemic tissues, causing severe inflammation of serosas by cytokine activation and attraction of phagocytes. A serum antibody response is usually present in pigs surviving systemic infection or after vaccination and is highly associated with protection against H. parasuis disease, even though heterologous protection is limited. Since antimicrobial use is widespread in the swine industry and antimicrobials are used as an option to control H. parasuis disease, their effects on the immune response need to be taken into account. While antibiotic treatment can be very effective at controlling H. parasuis infections, it may also interfere with the development of protective immune responses against H. parasuis. Therefore, an improved understanding of how H. parasuis primes a protective immune response and the specific roles of humoral and cellular immune responses in protection to H. parasuis disease are needed. An improved understanding on the effect of antimicrobials on the immune response will contribute to the development of better control programs for H. parasuis and will help develop judicious antibiotic treatment practices.

Abbreviations

PRR: 

pattern-recognition receptor

TLR: 

toll-like receptor

PAMP: 

pathogen-associated molecular pattern

PAM: 

porcine alveolar macrophage

vtaA: 

virulent-associated trimeric autotransporter

IL: 

interleukin

TNF: 

tumor necrosis factor

IFN: 

interferon

Th: 

T helper cells

LPS: 

lipopolysaccharides

Ig: 

immunoglobulin

PMN: 

polymorphonuclear leukocytes

Declarations

Authors’ contributions

NM, AR, MT—all contributed in writing the manuscript. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
College of Veterinary Medicine, University of Minnesota

References

  1. Aragon V, Segales J, Oliveira S (2012) Glasser’s disease. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz K, Stevenson GW (eds) Diseases of swine. Wiley, New YorkGoogle Scholar
  2. Cerdà-Cuéllar M, Naranjo JF, Verge A, Nofrarias M, Cortey M, Olvera A, Aragon V (2010) Sow vaccination modulates the colonization of piglets by Haemophilus parasuis. Vet Microbiol 145:315–320View ArticlePubMedGoogle Scholar
  3. Macedo N, Rovira A, Oliveira S, Holtcamp A, Torremorell M (2014) Enrofloxacin treatment affects the colonization stage of Haemophilus parasuis in weaned pigs. Can J Vet Res 78:17–22PubMed CentralPubMedGoogle Scholar
  4. Olvera A, Segales J, Aragon V (2007) Update on the diagnosis of Haemophilus parasuis infection in pigs and novel genotyping methods. Vet J 174:522–529View ArticlePubMedGoogle Scholar
  5. Miniats OP, Smart NL, Rosendal S (1991) Cross protection among Haemophilus parasuis strains in immunized gnotobiotic pigs. Can J Vet Res 55:37–41PubMed CentralPubMedGoogle Scholar
  6. Bak H, Riising HJ (2002) Protection of vaccinated pigs against experimental infections with homologous and heterologous Haemophilus parasuis. Vet Rec 151:502–505View ArticlePubMedGoogle Scholar
  7. Oliveira S, Pijoan C (2004) Haemophilus parasuis: new trends on diagnosis, epidemiology and control. Vet Microbiol 26:1–12View ArticleGoogle Scholar
  8. Takahashi K, Naga S, Yagihashi T, Ikehata T, Nakano Y, Senna K, Maruyama T, Murofushi J (2001) A cross-protection experiment in pigs vaccinated with Haemophilus parasuis serovars 2 and 5 bacterins, and evaluation of a bivalent vaccine under laboratory and field conditions. J Vet Med Sci 63:487–491View ArticlePubMedGoogle Scholar
  9. Yu Y, Wu G, Zhai Z, Yao H, Lu C, Zhang W (2015) Fifteen novel immunoreactive proteins of Chinese virulent Haemophilus parasuis serotype 5 verified by an immunoproteomic assay. Folia Microbiol (Praha) 60:81–87View ArticleGoogle Scholar
  10. Fu S, Yuan F, Zhang M, Tan C, Chen H, Bei W (2012) Cloning, expression and characterization of a cell wall surface protein, 6-phosphogluconate dehydrogenase, of Haemophilus parasuis. Res Vet Sci 93:57–62View ArticlePubMedGoogle Scholar
  11. Hong M, Ahn J, Yoo S, Hong J, Lee E, Yoon I, Jung JK, Lee H (2011) Identification of novel immunogenic proteins in pathogenic Haemophilus parasuis based on genome sequence analysis. Vet Microbiol 148:89–92View ArticlePubMedGoogle Scholar
  12. Olvera A, Pina S, Pérez-Simó M, Oliveira S, Bensaid A (2010) Virulence-associated trimericautotransporters of Haemophilus parasuis are antigenic proteins expressed in vivo. Vet Res 41:26–37PubMed CentralView ArticlePubMedGoogle Scholar
  13. Yuan F, Fu S, Hu J, Li J, Chang H, Hu L, Chen H, Tian Y, Bei W (2012) Evaluation of recombinant proteins of Haemophilus parasuis strain SH0165 as vaccine candidates in a mouse model. Res Vet Sci 93:51–56View ArticlePubMedGoogle Scholar
  14. Martínez-Martínez S, Frandoloso R, Rodriguez Ferri EF, Gil C, Hernandez-Haro C, Yubero S, Gutierrez Martin CB (2013) Immunoproteomic analysis of the protective response obtained with subunit and commercial vaccines against Glässer’s disease in pigs. Vet Immunol Immunopathol 151:235–247View ArticlePubMedGoogle Scholar
  15. Nielsen P, Gyrd-Hansen N (1997) Bioavailability of enrofloxacin after oral administration to fed and fasted pigs. Pharmacol Toxicol 80:246–250View ArticlePubMedGoogle Scholar
  16. Hooper DC (2001) Mechanisms of action of antimicrobials: focus on fluoroquinolones. Clin Infect Dis 32:S9–S15View ArticlePubMedGoogle Scholar
  17. Dayao DAE, Kienzle M, Gibson JS, Blackall PJ, Turni C (2014) Use of a proposed antimicrobial susceptibility testing method for Haemophilus parasuis. Vet Microbiol 172:586–589View ArticlePubMedGoogle Scholar
  18. Martin de la Fuente AJ, Tucker AW, Navas J, Blanco M, Morris SJ, Gutierrez-Martin CB (2007) Antimicrobial susceptibility patterns of Haemophilus parasuis from pigs in the United Kingdom and Spain. Vet Microbiol 120:184–191View ArticleGoogle Scholar
  19. Zhou X, Xu X, Zhao Y, Chen P, Zhang X, Chen H, Cai X (2010) Distribution of antimicrobial resistance among different serovars of Haemophilus parasuis isolates. Vet Microbiol 141:168–173View ArticlePubMedGoogle Scholar
  20. Sjolund M, Fossum C, Martín de la Fuente AJ, Alava M, Juul-Madsen HR, Lampreave F, Wallgren P (2009) Response of pigs to a re-challenge with Actinobacillus pleuropneumoniae after being treated with different antimicrobials following their initial exposure. Vet Rec 164:550–555View ArticlePubMedGoogle Scholar
  21. Su H, Morrison R, Messer R, Whitmire W, Hughes S, Caldwell HD (1999) The effect of doxycycline treatment on the development of protective immunity in a murine model of chlamydial genital infection. J Infect Dis 180:1252–1258View ArticlePubMedGoogle Scholar
  22. Griffin A, Baraho-Hassan D, McSorley SJ (2009) Successful treatment of bacterial infection hinders development of acquired immunity. J Immunol 183:1263–1270PubMed CentralView ArticlePubMedGoogle Scholar
  23. Chase CCL, Lunney JK (2012) Immune system. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz K, Stevenson GW (eds) Disease of swine. Wiley, New YorkGoogle Scholar
  24. Uenishi H, Shinkai H (2009) Porcine Toll-like receptors: the front line of pathogen monitoring and possible implications for disease resistance. Dev Comp Immunol 33:353–361View ArticlePubMedGoogle Scholar
  25. Kindt TJ, Goldsby RA, Osborne BA (2007) Innate and adaptive immunity. In: Kindt TJ, Goldsby RA, Osborne BA (eds) Kuby immunolgy. Freeman and Company, New YorkGoogle Scholar
  26. Takamatisu HH, Denyer MS, Stirling C, Cox S, Aggarwal N, Dash P, Wileman TE, Barnett PV (2006) Porcine γδ T cells: possible roles on the innate and adaptive immune responses following virus infection. Vet Immunol Immunopathol 112:49–61View ArticleGoogle Scholar
  27. Butler JE, Wertz N, Deschacht N, Kacskovics I (2009) Porcine IgG: structure, genetics, and evolution. Immunogenetics 61:209–230View ArticlePubMedGoogle Scholar
  28. Piriou-Guzylack L, Salmon H (2008) Membrane markers of the immune cells in swine: an update. Vet Res 39:54View ArticlePubMedGoogle Scholar
  29. Fairbairn L, Kapetanovic R, Beraldi D, Sester DP, Tuggle CK, Archibald AL, Hume DH (2013) Comparative analysis of monocytes subsets in the pig. J Immunol 190:6389–6396View ArticlePubMedGoogle Scholar
  30. Olvera A, Ballester M, Nofrarías M, Sibila M, Aragon V (2009) Differences in phagocytosis susceptibility in Haemophilus parasuis strains. Vet Res 40:24–36PubMed CentralView ArticlePubMedGoogle Scholar
  31. Wang Y, Liu C, Fang Y, Liu X, Li W, Liu S, Liu Y, Liu Y, Charreyre C, Audonnet JC, Chen P, He Q (2012) Transcription analysis on response of porcine alveolar macrophages to Haemophilus parasuis. BMC Genomics 13:68PubMed CentralView ArticlePubMedGoogle Scholar
  32. Costa-Hurtado M, Olvera A, Martinez-Moliner V, Galofré-Milà N, Martínez P, Dominguez J, Aragon V (2013) Changes in macrophage phenotype after infection of pigs with Haemophilus parasuis strains with different levels of virulence. Infect Immun 81:2327–2333PubMed CentralView ArticlePubMedGoogle Scholar
  33. Costa-Hurtado M, Ballester M, Galofré-Milà N, Darji A, Aragon V (2012) VtaA 8 and VtaA 9 from Haemophilus parasuis delay phagocytosis by alveolar macrophages. Vet Res 27:43–57Google Scholar
  34. Segalés J, Domingo M, Solano GI, Pijoan C (1997) Immunohistochemical detection of Haemophilus parasuis serovar 5 in formalin-fixed, paraffin-embedded tissues of experimentally infected swine. J Vet Diagn Invest 9:237–243View ArticlePubMedGoogle Scholar
  35. Amano H, Shibata M, Kajio N, Morozumi T (1994) Pathologic observations of pigs intranasally inoculated with serovar 1, 4 and 5 of Haemophilus parasuis using immunoperoxidase method. J Vet Med Sci 56:639–644View ArticlePubMedGoogle Scholar
  36. Bouchet B, Vanier G, Jacques M, Gottschalk M (2008) Interactions of Haemophilus parasuis and its LOS with porcine brain microvascular endothelial cells. Vet Res 39:42View ArticlePubMedGoogle Scholar
  37. Bouchet B, Vanier G, Jacques M, Auger E, Gottschalk M (2009) Studies of the interactions of Haemophilus parasuis with porcine epithelial tracheal cells: limited role of LOS in apoptosis and pro-inflammatory cytokine release. Microb Pathog 46:108–113View ArticlePubMedGoogle Scholar
  38. Martin de la Fuente AJ, Ferri EF, Tejerina F, Frandoloso R, Martinez SM, Martin CB (2009) Cytokine expression in colostrum-deprived pigs immunized and challenged with Haemophilus parasuis. Res Vet Sci 87:47–52View ArticleGoogle Scholar
  39. Frandoloso R, Martinez-Martinez S, Yubero S, Rodriguez-Ferri EF, Gutierrez-Martin CB (2012) New insights in cellular immune response in colostrum-deprived pigs after immunization with subunit and commercial vaccines against Glasser’s disease. Cell Immunol 277:74–82View ArticlePubMedGoogle Scholar
  40. Costa-Hurtado M, Aragon V (2013) Advances in the quest for virulence factors of Haemophilus parasuis. Vet J 198:571–576View ArticlePubMedGoogle Scholar
  41. Zhang B, Xu C, Liao M (2012) Outer membrane protein P2 of the Haemophilus parasuis SC096 strain contributes to adherence to porcine alveolar macrophages cells. Vet Microbiol 158:226–227View ArticlePubMedGoogle Scholar
  42. Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146View ArticlePubMedGoogle Scholar
  43. Murtaugh MP, Johnson CR, Xiao Z, Scamurra RW, Zhou Y (2009) Species specialization in cytokine biology: is interleukin-4 central to the Th1–Th2 paradigm in swine? Dev Comp Immunol 33:344–352View ArticlePubMedGoogle Scholar
  44. Martin de la Fuente AJ, Gutierrez-Martin CB, Rodriguez-Barbosa JL, Martinez-Martinez S, Frandoloso S, Tejerina F, Rodriguez-Ferri EF (2009) Blood cellular immune response in pigsimmunized and challenged with Haemophilus parasuis. Res Vet Sci 86:230–234View ArticleGoogle Scholar
  45. Martin de la Fuente AJ, Rodriguez-Ferri EF, Frandoloso R, Martinez S, Tejerina F, Gutierrez-Martin CB (2009) Systemic antibody response in colostrum-deprived pigs experimentally infected with Haemophilus parasuis. Res Vet Sci 86:248–253View ArticlePubMedGoogle Scholar
  46. Nedbalcova K, Kucerova Z, Krejci J, Tesarik R, Gopfert E, Kummer V, Leva L, Kudlackova H, Ondriasova R, Faldyna M (2011) Passive immunization of post-weaned piglets using hyperimmune serum against experimental Haemophilus parasuis infection. Res Vet Med 91:225–229Google Scholar
  47. Bello-Ortí B, Deslandes V, Tremblay YD, Labrie J, Howell KJ, Tucker AW, Maskell DJ, Aragon V, Jacques M (2014) Biofilm formation by virulent and non-virulent strains of Haemophilus parasuis. Vet Res 45:104PubMed CentralView ArticlePubMedGoogle Scholar
  48. Cerda-Cuellar M, Aragon V (2008) Serum-resistance in Haemophilus parasuis is associated with systemic disease in swine. Vet J 175:384–389View ArticlePubMedGoogle Scholar
  49. Schoevers EJ, van Leengoed LA, Verheijden JH, Niewold TA (1999) Effects of enrofloxacin on porcine phagocytic function. Antimicrob Agents Chemother 43:2138–2143PubMed CentralPubMedGoogle Scholar
  50. Oliveira S, Batista L, Torremorell M, Pijoan C (2001) Experimental colonization of piglets and gilts with systemic strains of Haemophilus parasuis and Streptococcus suis to prevent disease. Can J Vet Res 65:161–167PubMed CentralPubMedGoogle Scholar
  51. Oliveira S, Pijoan C, Morrison R (2001) Evaluation of Haemophilus parasuis control in the nursery using vaccination and controlled exposure. J Swine Health Prod 2:123–128Google Scholar

Copyright

© Macedo et al. 2015