Histoplasma capsulatummanifests preferential invasion of phagocytic subpopulations in murine lungs

Abstract

Numerous in vitro studies have demonstrated that Histoplasma capsulatum is engulfed by the diverse populations of phagocytic cells including monocytes/macrophages (Mphi), immature dendritic cells (DC), and neutrophils. The in vivo distribution of H. capsulatum has yet to be examined following an intrapulmonary challenge. To accomplish this goal, we engineered GFP into two genetically dissimilar strains of H. capsulatum, G217B and 186R. C57BL/6 mice were infected with each of these strains, and we analyzed the distribution of this fungus in the three major phagocytic populations on successive days. Yeast cells were found in all three populations of cells from Days 1 through 7. Proportionally, DC dominated at Day 1, whereas the majority of yeast cells was detected in neutrophils thereafter. Yeast cells were present in inflammatory and resident Mphi on Day 3, but on Day 7, they were chiefly in inflammatory Mphi. Yeast cells were predominantly in a CD11c(+intermediate/high), F4/80(-), CD11b(+), Ly-6C(+), CD205(+) DC population. Neutralization of TNF-alpha or IFN-gamma produced a significant redistribution of yeast cells. These results reveal the complex nature of intracellular residence of this fungus. Moreover, the findings demonstrate that there is a skewing in the subpopulations of cells that are infected, especially DC.

Monoclonal Antibodies to Heat Shock Protein 60 Alter the Pathogenesis ofHistoplasma capsulatum

“…capsulatum by mechanisms dependent on hydrogen peroxide and products of the nitric oxide synthase pathway, whereas fungistasis depends largely on products of the nitric oxide synthase pathway (6). Different MAbs can change the skew in the subpopulations of cells that are infected and the distribution of the fungus, as well as the induction of different effector cell populations, resulting in different outcomes of inflammation and reduction of the fungal burden in infected organs (13). Hence, despite their protective effect, the IgG1 and IgG2a MAbs did not prevent disseminated disease but modified the host response to the fungus in pleotropic ways.…”

Methamphetamine Enhances Histoplasmosis by Immunosuppression of the Host

“…Additionally, methamphetamine-treated mice lost weight with treatment at physiological doses. During the early phase of histoplasmosis, macrophages recognize and phagocytose H. capsulatum [31], thereby providing the fungus access to a intracellular environment that is permissive for replication. This initial interaction is crucial for the pathogenesis of histoplasmosis.…”

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…Within the macrophages, the yeast replicates, destroying the macrophages and is subsequently taken up by surrounding neutrophils, inflammatory macrophages and DCs. 40 This leads to spread of the infection to lymph nodes and other organs during the acute stage of primary histoplasmosis. Consequently the resultant development of cell-mediated immunity against.…”