The early interferon response of nasal-associated lymphoid tissue to Streptococcus pyogenes infection.
Streptococcus pyogenes is a major causative agent of tonsillitis or pharyngitis in children. Streptococcus pyogenes can persist in tonsils, and one-third of children treated with antibiotics continue to shed streptococci and have recurrent infections. Mouse nasal-associated lymphoid tissue (NALT) is functionally analogous to human oropharyngeal lymphoid tissues, and serves as a model for characterization of the mucosal innate immune response to S. pyogenes. Wild-type S. pyogenes induces transcription of both type I and interferon-gamma (IFN-gamma)-responsive genes, proinflammatory genes and acute-phase response proteins 24 h after intranasal infection. Invasion of NALT and the induction of the interferon response were not dependent on expression of antiphagocytic M protein. Intranasal infection induces a substantial influx of neutrophils into NALT at 24 h, which declines by 48 h after infection. Infection of IFN-gamma(-/-) [IFN-gamma knock-out mouse (GKO)] C57BL/6 mice with wild-type S. pyogenes resulted in local dissemination of bacteria to draining lymph nodes (LN), but did not lead to systemic infection by 48 h after infection. Infected GKO mice had an increased influx of neutrophils into NALT compared with immunocompetent mice. Thus, IFN-gamma-induced responses are required to prevent local dissemination of streptococci to the draining LN.
Hyland
Kendra A
KA
Department of Microbiology, University of Minnesota, Minneapolis, MN 55413, USA. hyla0021@umn.edu
Brennan
Robert
R
Olmsted
Stephen B
SB
Rojas
Eduardo
E
Murphy
Ellen
E
Wang
Beinan
B
Cleary
P Patrick
PP
D000818:Animals; D002470:Cell Survival; D015169:Colony Count, Microbial; D005260:Female; D020869:Gene Expression Profiling; D007372:Interferons / Q000096:biosynthesis* / Q000172:deficiency; D008198:Lymph Nodes / Q000382:microbiology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*
D007372:Interferons