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Originally published online as doi:10.1189/jlb.0308154 on June 24, 2008

Published online before print June 24, 2008
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(Journal of Leukocyte Biology. 2008;84:669-678.)
© 2008 by Society for Leukocyte Biology

Histoplasma capsulatum manifests preferential invasion of phagocytic subpopulations in murine lungs

George S. Deepe, Jr*,{dagger},1, Reta S. Gibbons{dagger} and A. George Smulian*,{dagger}

* Veterans Affairs Hospital and
{dagger} Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

1 Correspondence: Division of Infectious Diseases, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0560, USA. E-mail: george.deepe{at}uc.edu

ABSTRACT

Numerous in vitro studies have demonstrated that Histoplasma capsulatum is engulfed by the diverse populations of phagocytic cells including monocytes/macrophages (M{phi}), 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 and186R. 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 M{phi} on Day 3, but on Day 7, they were chiefly in inflammatory M{phi}. 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.

Key Words: rodent • fungus • innate immunity




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