1. Monocyte Production of C1q Potentiates CD8 + T-Cell Function Following Respiratory Viral Infection.
- Author
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Eddens T, Parks OB, Lou D, Fan L, Sojati J, Ramsey MJ, Schmitt L, Salgado CM, Reyes-Mugica M, Evans A, Zou HM, Oury TD, Byersdorfer C, Chen K, and Williams JV
- Subjects
- Animals, Humans, Mice, Metapneumovirus immunology, COVID-19 immunology, COVID-19 virology, COVID-19 pathology, COVID-19 metabolism, Complement C1q metabolism, Complement C1q genetics, SARS-CoV-2 immunology, Mice, Inbred C57BL, Interferon-gamma metabolism, Lymphocyte Activation immunology, Respiratory Tract Infections immunology, Respiratory Tract Infections virology, Respiratory Tract Infections pathology, Respiratory Tract Infections metabolism, Paramyxoviridae Infections immunology, Paramyxoviridae Infections virology, Paramyxoviridae Infections metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Monocytes immunology, Monocytes metabolism
- Abstract
Respiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus, we identified recruitment of a C1q-expressing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8
+ T-cell function. Production of C1q by a myeloid lineage was necessary to enhance CD8+ T-cell function. Activated and dividing CD8+ T cells expressed a C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD8+ T-cell IFN-γ production, metabolic capacity, and cell proliferation. Autopsy specimens from fatal respiratory viral infections in children exhibited diffuse production of C1q by an interstitial population. Humans with severe coronavirus disease (COVID-19) infection also exhibited upregulation of gC1qR on activated and rapidly dividing CD8+ T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD8+ T-cell function following respiratory viral infection.- Published
- 2024
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