Biology subjects

Yipp, B. G.

Publications and source records attributed to Yipp, B. G..

2 recordsLinked to original sources

bioRxiv2024

β-Glucan Reprograms Neutrophils to Induce Disease Tolerance Against Influenza A Virus

ABSTRACTDisease tolerance is an evolutionarily conserved host defence strategy that preserves tissue integrity and physiology without affecting pathogen load. Unlike host resistance, the mechanisms underlying disease tolerance remain poorly understood. In the present study, we investigated whether an adjuvant ({beta}-glucan) can reprogram innate immunity to provide protection against Influenza A virus (IAV) infection. Here we observe that {beta}-glucan treatment reduced the morbidity and mortality against IAV infection, independent of host resistance (viral load). Increased survival of {beta}-glucan treated mice against IAV is associated with the accumulation of neutrophils via RoR{gamma}t+ T cells in the lung tissue. Using gain-and-loss-of-function approaches, we demonstrate that {beta}- glucan reprogrammed neutrophils are essential for promoting disease tolerance, limiting pulmonary tissue damage, and enhancing survival against IAV infection. {beta}-glucan treatment promotes granulopoiesis in a type 1 interferon-dependent manner that leads to the generation of a unique subset of neutrophils, which are less mature with higher mitochondrial mass utilizing mitochondrial oxidative (OXPHOS) metabolism. Collectively, our data indicate that {beta}-glucan reprograms hematopoietic stem cells (HSCs) to generate neutrophils with a novel "regulatory" function, which is required for promoting disease tolerance and maintaining lung tissue integrity against viral infection.

immunology↗

bioRxiv2024

Vagal TRPV1+ sensory neurons regulate myeloid cell dynamics and protect against influenza virus infection

Influenza viruses are a major global cause of morbidity and mortality. Vagal TRPV1+ nociceptive sensory neurons, which innervate the airways, are known to mediate defenses against harmful agents. However, their function in lung antiviral defenses remains unclear. Our study reveals that both systemic and vagal-specific ablation of TRPV1+ nociceptors reduced survival in mice infected with influenza A virus (IAV), despite no significant changes in viral burden or weight loss. Mice lacking nociceptors showed exacerbated lung pathology and elevated levels of pro-inflammatory cytokines. The increased mortality was not attributable to the loss of the TRPV1 ion channel or neuropeptides CGRP or substance P. Immune profiling through flow cytometry and single-cell RNA sequencing identified significant nociceptor deficiency-mediated changes in the lung immune landscape, including an expansion of neutrophils and monocyte-derived macrophages. Transcriptional analysis revealed impaired interferon signaling in these myeloid cells and an imbalance in distinct neutrophil sub-populations in the absence of nociceptors. Furthermore, anti-GR1-mediated depletion of myeloid cells during IAV infection significantly improved survival, underscoring a role of nociceptors in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality. One Sentence Summary: TRPV1+ neurons facilitate host survival from influenza A virus infection by controlling myeloid cell responses and immunopathology.

immunology↗