Effect of immune serum and role of individual Fcγ receptors on the intracellular distribution and survival of Salmonella enterica serovar Typhimurium in murine macrophages

Abstract

SummaryImmune serum has a protective role against Salmonella infections in mice, domestic animals and humans. In this study, the effect of antibody on the interaction between murine macrophages and S. enterica serovar Typhimurium was examined. Detailed analysis at the single-cell level demonstrated that opsonization of the bacteria with immune serum enhanced bacterial uptake and altered bacterial distribution within individual phagocytic cells. Using gene-targeted mice deficient in individual Fc gamma receptors it was shown that immune serum enhanced bacterial internalization by macrophages via the high-affinity immunoglobulin G (IgG) receptor, Fc gamma receptor I. Exposure of murine macrophages to S. enterica serovar Typhimurium opsonized with immune serum resulted in increased production of superoxide, leading to enhanced antibacterial functions of the infected cells. However, opsonization of bacteria with immune serum did not increase either nitric oxide production in response to S. enterica serovar Typhimurium or fusion of phagosomes with lysosomes.

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.…”

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

“…Although mouse complement has limited bactericidal activity (19,20), adoptive transfer studies (21,22) and studies in T cell-deficient mice (23,24) demonstrate the importance of antibody in immunity against Salmonella. Antibody is required for phagocytosis, oxidative burst function, and cellular killing of Salmonella by mouse macrophages (25).…”

The essential role of complement in antibody‐mediated resistance to Salmonella

“…In fact, protection against oral infection in immunized animals, which is IgG dependent,10 does not require the C3 component of complement, but is dependent on the function of Fc γ RI, II and III 4. Moreover, uptake and killing of IgG‐opsonized Salmonella by murine macrophages and human phagocytic cell lines can be mediated by Fc γ Rs in the absence of complement 5, 6, 7. However, poor complement activity has been inferred to be the cause of the poor antibody‐dependent bactericidal activity of mouse serum against non‐typhoidal strains of Salmonella 8.…”