Alternatively activated lung alveolar and interstitial macrophages promote fungal growth

Ashley B Strickland; Yanli Chen; Donglei Sun; Meiqing Shi

doi:10.1016/j.isci.2023.106717

Alternatively activated lung alveolar and interstitial macrophages promote fungal growth

iScience. 2023 Apr 23;26(5):106717. doi: 10.1016/j.isci.2023.106717. eCollection 2023 May 19.

Authors

Ashley B Strickland¹, Yanli Chen¹, Donglei Sun¹, Meiqing Shi¹

Affiliation

¹ Division of Immunology, Virginia-Maryland College of Veterinary Medicine, Maryland Pathogen Research Institute, University of Maryland, College Park, MD 20742, USA.

Abstract

How lung macrophages, especially interstitial macrophages (IMs), respond to invading pathogens remains elusive. Here, we show that mice exhibited a rapid and substantial expansion of macrophages, especially CX3CR1⁺ IMs, in the lung following infection with Cryptococcus neoformans, a pathogenic fungus leading to high mortality among patients with HIV/AIDS. The IM expansion correlated with enhanced CSF1 and IL-4 production and was affected by the deficiency of CCR2 or Nr4a1. Both alveolar macrophages (AMs) and IMs were observed to harbor C. neoformans and became alternatively activated following infection, with IMs being more polarized. The absence of AMs by genetically disrupting CSF2 signaling reduced fungal loads in the lung and prolonged the survival of infected mice. Likewise, infected mice depleted of IMs by the CSF1 receptor inhibitor PLX5622 displayed significantly lower pulmonary fungal burdens. Thus, C. neoformans infection induces alternative activation of both AMs and IMs, which facilitates fungal growth in the lung.

Keywords: Biological sciences; Cell biology; Immunology; Mycology.