TLR2-, TLR4- and Myd88-independent acquired humoral and cellular immunity against Salmonella enterica serovar Typhimurium.
Toll-like receptors (TLR) are central to pathogen recognition by the innate immune system. However, their role in the generation of acquired immunity is less clear. Using experimental Salmonella enterica serovar Typhimurium (ST) infection of mice, we determined the role of TLR2, TLR4 and of the TLR adaptor protein Myeloid differentiation factor 88 (MyD88) in the generation of specific T- and B-cell responses against this pathogen. When infected with an attenuated ST strain, mice deficient in TLR4, TLR2 plus TLR4 or MyD88 suffered from exacerbated bacterial burden and delayed clearance. However, all mutant mice not only survived infection but also generated normal antibody responses. Compared to wild-type mice, TLR2+4 deficient mice displayed even enhanced CD4(+) T(H)1 and CD8(+) T cell responses. In contrast, T-cell responses in TLR2 deficient and MyD88 deficient mice were similar to those observed in wild-type controls. Overall, T- and B-cell responses were functional and provided protection against a challenge infection with virulent ST. Our results demonstrate that in the ST infection model, MyD88 as well as TLR2 and TLR4 were largely dispensable for the induction of protective acquired immunity.
Seibert
Sabine A
SA
Max-Planck-Institute for Infection Biology, Department of Immunology, Charitéplatz 1, D-10117 Berlin, Germany.
Mex
Peggy
P
Köhler
Anne
A
Kaufmann
Stefan H E
SH
Mittrücker
Hans-Willi
HW
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002469:Cell Separation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000097:blood / Q000276:immunology*; D019779:Salmonella enterica / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014774:Virulence
D000907:Antibodies, Bacterial; D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4