Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 10, Pages 6340-6345Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.10.6340
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- NIAID NIH HHS [AI-27828] Funding Source: Medline
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Previous studies have shown that the in vitro ligation of Fc gamma Rs with IgG-opsonized Leishmania amastigotes promotes IL-10 production by macrophages. In addition, infection of either BALB/c mice lacking the common gamma-chain of Fc receptors (Fc gamma R-/-) or mice genetically altered to lack circulating Ab (J(H)D) with Leishmania pifanoi results in reduced and delayed lesion development and a deficit in the recruitment of inflammatory cells into infected lesions. We show in this study that Fc gamma R-/- mice can control infection with Leishmania major and totally resolve cutaneous lesions. The ability to eventually control infection is not associated with a reduction in lesion inflammation or a reduction in the ability of Leishmania to parasitize cells through week 6 of infection. The immune response in healing Fc gamma R-/- mice is associated with a reduction in numbers of, cells producing Th2-type cytokines, including IL-4 and IL-10, but not an increase in numbers of IFN-gamma-producing cells characteristic of a dominant Th1-type response. Instead, we observe a reduction in levels of IL-10 and TGF-beta within infected lesions, including reduced levels of these cytokines within parasitized macrophages. Together, these results suggest that uptake of opsonized parasites via Fc gamma Rs may be a strong in vivo stimulus for the production of anti-inflammatory cytokines that play a role in susceptibility to infection.
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