Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis

Abstract

We show here that maintenance of Leishmania infections with Leishmania mexicana complex parasites (Leishmania amazonensis and Leishmania pifanoi) is impaired in the absence of circulating antibody. In these studies, we used mice genetically altered to contain no circulating antibody, with and without functional B cells. This experimental design allowed us to rule out a critical role for B cell antigen presentation in Leishmania pathogenesis. In addition, we show that mice lacking the common γ chain of Fc receptors (FcγRI, FcεRI, and FcγRIII) are similarly refractory to infection with these parasites. These observations establish a critical role for antibody in the pathogenesis associated with infection by members of the L. mexicana complex.

Fcγ Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection

“…Deficiency of the Fc␥-chain was previously reported to affect the progression of infection with other intracellular pathogens, including influenza and Leishmania species (17)(18)(19)(20)(21)(22). Diminished survival was associated with statistically significantly elevated bacterial burden in the lungs and spleens 15 wk, but not 3 wk, after infection.…”

“…Other reports have previously implicated Fc␥R as affecting host defense in infectious disease models (17)(18)(19)(20)(21)(22)47). Interestingly, lupus-associated polymorphisms in Fc␥RIIB have been correlated with reduced susceptibility to malaria in humans (21), suggesting that infectious diseases may provide selective pressure for autoimmunity.…”

“…Separated into activating and inhibiting types, Fc␥R mediate immune activation or suppression based upon a threshold determined by the summation of their reciprocal signals (16). Murine models of Fc␥R deficiency have been useful in assessing the relevance of these receptors against intracellular pathogens, including Chlamydia trachomatis, influenza virus, Leishmania species, Plasmodium, and Salmonella enterica (17)(18)(19)(20)(21)(22). However, no such study had yet been conducted with M. tuberculosis, possibly because of the prevailing view that humoral immunity has little or no role in host defense against this pathogen.…”

Neuroinvasion by a Creutzfeldt–Jakob disease agent in the absence of B cells and follicular dendritic cells

“…Interestingly, IgG Abs were also reduced in all other mutants reported to delay progressive scrapie infection. It is known, moreover, that IgG binding to Ags and pathogens can markedly enhance the ability of macrophages and dendritic cells to take up Ags and pathogens by means of Fc receptors, as shown for example with Leishmania mexicana (30). Thus, IgG Abs could enhance agent uptake into myeloid cells, which may in turn heighten agent replication (22,31).…”

PD‐L1 and PD‐L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis

“…In addition, the humoral response is important in the pathogenesis of L. mexicana. Leishmania-specific antibodies may facilitate parasite entry into macrophages [20]. Opsonized L. mexicana amastigotes also promote IL-10 production by macrophages.…”