Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes.
Mice deficient in lymphocytes are more resistant than normal mice to Listeria monocytogenes infection during the early innate immune response. This paradox remains unresolved: lymphocytes are required for sterilizing immunity, but their presence during the early stage of the infection is not an asset and may even be detrimental. We found that lymphocyte-deficient mice, which showed limited apoptosis in infected organs, were resistant during the first four days of infection but became susceptible when engrafted with lymphocytes. Engraftment with lymphocytes from type I interferon receptor-deficient (IFN-alphabetaR(-/-)) mice, which had reduced apoptosis, did not confer increased susceptibility to infection, even when the phagocytes were IFN-alphabetaR(+/+). The attenuation of innate immunity was due, in part, to the production of the antiinflammatory cytokine interleukin 10 by phagocytic cells after the apoptotic phase of the infection. Thus, immunodeficient mice were more resistant relative to normal mice because the latter went through a stage of lymphocyte apoptosis that was detrimental to the innate immune response. This is an example of a bacterial pathogen creating a cascade of events that leads to a permissive infective niche early during infection.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Javier A
JA
Carrero
Boris
B
Calderon
Emil R
ER
Unanue
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007370:Interferon Type I / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D013154:Spleen / Q000382:microbiology / Q000473:pathology
D004268:DNA-Binding Proteins; D007370:Interferon Type I; C499308:Rag2 protein, mouse; D016753:Interleukin-10