Pretreatment with probioticL. johnsoniiL531 protects the intestine fromS. Infantis infection by regulating ER protein expression and CCR6+T-cell responses.Salmonella Infantis infection is usually associated with dysbiosis . Intragastric administration of L. johnsonii L531 decreased the abundance of total bacteria and reduced the colonization of Salmonella in the intestine . During S. Infantis infection, L. johnsonii L531 attenuates ER stress and inhibits the production of lipocalin 2 in the intestine. In the intestinal mesenteric lymph nodes, S. Infantis elevated the proportion of CCR6+ IFNγ+ T cells, and L. johnsonii L531 induced an increase in CD4+ CCR6+ T cells in response to S. Infantis challenge. Challenge with S. Infantis decreased the percentage of CD4− CCR6+ T cells but increased the percentage of CCR6− IFNγ+ T cells in peripheral blood. The Salmonella-associated ER stress ameliorated by L. johnsonii L531 and its regulation of T cell responses during S. Infantis infection contribute to inhibition of inflammation development and maintenance of intestinal homeostasis.