Neutrophils Restrain CCR2-Dependent Monocyte Immunopathology During Pulmonary Cryptococcosis.
- 1The University of Tennessee Health Science Center
Abstract
Neutrophils are essential for host defense against most invasive fungal pathogens, yet their role in cryptococcosis remains paradoxical. Neutropenia is not a recognized risk factor for cryptococcal disease, and an early study reported that neutrophil depletion improves survival in mice, supporting the prevailing view that these cells are dispensable. Here we re-examined this question using Ly6G-specific depletion strategies. Contrary to prior reports, neutrophil-depleted mice infected with Cryptococcus neoformans succumbed significantly more rapidly than isotype-treated controls. Accelerated mortality occurred without any increase in pulmonary fungal burden at 24h, 48h, or day 7, or in brain and spleen at day 7, indicating host-mediated rather than pathogen-driven death. This phenotype was independent of mouse genetic background, depletion antibody, inoculum, and fungal strain. Within 24h, neutrophil depletion provoked an early chemokine and IL-17A response, followed by pronounced pulmonary accumulation of inflammatory monocytes and macrophages by day 7. Strikingly, the increased mortality associated with neutrophil depletion was completely absent in Ccr2-/- mice, implicating CCR2-dependent inflammatory responses in disease severity. Together, these findings reveal a previously underappreciated protective function of neutrophils during cryptococcosis, whereby they constrain inflammatory monocyte-associated immunopathology and promote host survival independently of measurable changes in fungal burden.
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BibTeX
@misc{hardenpruitt2026neutrophils,
title = {{Neutrophils Restrain CCR2-Dependent Monocyte Immunopathology During Pulmonary Cryptococcosis.}},
author = {M. C. Harden-Pruitt and R. G. Rebekah and C. R. Hole},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.26.762039},
url = {https://www.biorxiv.org/content/10.64898/2026.10.26.762039v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Neutrophils Restrain CCR2-Dependent Monocyte Immunopathology During Pulmonary Cryptococcosis.
AU - M. C. Harden-Pruitt
AU - R. G. Rebekah
AU - C. R. Hole
PY - 2026
DA - 2026/10/26
PB - bioRxiv
DO - 10.64898/2026.10.26.762039
UR - https://www.biorxiv.org/content/10.64898/2026.10.26.762039v1
AB - Neutrophils are essential for host defense against most invasive fungal pathogens, yet their role in cryptococcosis remains paradoxical. Neutropenia is not a recognized risk factor for cryptococcal disease, and an early study reported that neutrophil depletion improves survival in mice, supporting the prevailing view that these cells are dispensable. Here we re-examined this question using Ly6G-specific depletion strategies. Contrary to prior reports, neutrophil-depleted mice infected with Cryptococcus neoformans succumbed significantly more rapidly than isotype-treated controls. Accelerated mortality occurred without any increase in pulmonary fungal burden at 24h, 48h, or day 7, or in brain and spleen at day 7, indicating host-mediated rather than pathogen-driven death. This phenotype was independent of mouse genetic background, depletion antibody, inoculum, and fungal strain. Within 24h, neutrophil depletion provoked an early chemokine and IL-17A response, followed by pronounced pulmonary accumulation of inflammatory monocytes and macrophages by day 7. Strikingly, the increased mortality associated with neutrophil depletion was completely absent in Ccr2-/- mice, implicating CCR2-dependent inflammatory responses in disease severity. Together, these findings reveal a previously underappreciated protective function of neutrophils during cryptococcosis, whereby they constrain inflammatory monocyte-associated immunopathology and promote host survival independently of measurable changes in fungal burden.
SN - 2692-8205
ER -