Monocyte Production of C1q Potentiates CD8+ T-Cell Function Following Respiratory Viral Infection

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 CD81 T-cell function. Production of C1q by a myeloid lineage was necessary to enhance CD81 T-cell function. Activated and dividing CD81 T cells expressed a C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD81 T-cell IFN-g 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 CD81 T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD81 T-cell function following respiratory viral infection.