Histoplasma capsulatum manifests preferential invasion of phagocytic subpopulations in murine lungs

George S. Deepe, Jr^*^,^,1, Reta S. Gibbons and A. George Smulian^*^,

^* Veterans Affairs Hospital and
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 Histoplasmacapsulatum is engulfed by the diverse populations of phagocyticcells including monocytes/macrophages (M ${phi}$ ), immature dendriticcells (DC), and neutrophils. The in vivo distribution of H.capsulatum has yet to be examined following an intrapulmonarychallenge. To accomplish this goal, we engineered GFP into twogenetically dissimilar strains of H. capsulatum, G217B and186R.C57BL/6 mice were infected with each of these strains, and weanalyzed the distribution of this fungus in the three majorphagocytic populations on successive days. Yeast cells werefound in all three populations of cells from Days 1 through7. Proportionally, DC dominated at Day 1, whereas the majorityof yeast cells was detected in neutrophils thereafter. Yeastcells were present in inflammatory and resident M ${phi}$ on Day 3,but on Day 7, they were chiefly in inflammatory M ${phi}$ . Yeast cellswere 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 residenceof this fungus. Moreover, the findings demonstrate that thereis a skewing in the subpopulations of cells that are infected,especially DC.

Key Words: rodent • fungus • innate immunity