Work

Th2 immune responses promote anti-viral and anti-inflammatory activity during mild COVID-19 9405

Year: 2025

Type: article

Abstract: Description SARS-CoV-2 infected individuals frequently develop mild disease; however, the underlying mechanisms of improved outcomes are unknown. Using a training cohort, integrated clinical and molecular parameters revealed signatures that discriminated mild from moderate and severe outcomes. Early on, some mild individuals had higher antibody titer, lower viral loads, had allergic diseases and increased expression of Th2 cytokines. In contrast, moderate/severe individuals had higher viral loads, lower antibody titers, and increased IL-8, IP10 and IL-10 levels. A distinct blood transcriptional profile of these mild individuals suggested a mechanistic role for Th2 responses in modulating disease severity. Human tracheobronchial epithelial cells (HTBE) incubated with IL-4 and/or IL-13 to recapitulate a Th2 milieu in vitro, had increased levels of IFNγ, decreased SARS-CoV-2 replication, and inhibited IL-6 induction. IL-4 and IL-13 induced a differential gene expression profile that was not significantly altered upon SARS-CoV-2 infection. Multiome analysis of treated HTBEs showed an enrichment in the transcription factor binding sites of STAT6 and KLF4. Th2 treatment induced cell specific antiviral pathways, including SLC, autophagy and RAS genes, whereas pro-viral and inflammatory gene pathways, such as IL1B/IL6, cell cycle and transcription, were repressed. This suggests that during mild COVID-19, Th2 responses modulate early innate immune responses leading to the control of viral load. Funding Sources Supported by the FLUOMICS and SYBIL Consortium NIH-NIAID grant U19AI135972), Center for Research on Influenza Pathogenesis (CRIP), an NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C, FONDECYT 1212023 grant from ANID of Chile, Postdoctoral grants FONDECYT 3190706 and 3190648, ANID Becas/Doctorado Nacional 21212258. Topic Categories Viral Immunology (VIR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.2811