Neutrophils suppress mucosal‐associated invariant T cells in humans

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that are abundant in mucosal tissues and the liver where they can respond rapidly to a broad range of riboflavin producing bacterial and fungal pathogens. Neutrophils, which are recruited early to sites of infection, play a nonredundant role in pathogen clearance and are crucial for controlling infection. The interaction of these two cell types is poorly studied. Here, we investigated both the effect of neutrophils on MAIT cell activation and the effect of activated MAIT cells on neutrophils. We show that neutrophils suppress the activation of MAIT cells by a cell-contact and hydrogen peroxide dependent mechanism. Moreover, highly activated MAIT cells were able to produce high levels of TNF-α that induced neutrophil death. We therefore provide evidence for a negative regulatory feedback mechanism in which neutrophils prevent overactivation of MAIT cells and, in turn, MAIT cells limit neutrophil survival.Keywords: MAIT cells r Mucosal immunity r Neutrophils r TNF-α Additional supporting information may be found online in the Supporting Information section at the end of the article.

Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape

“…Ratio of circulating γδT to LDN cells has been suggested to correlate with COVID-19 severity and serves as an early marker of severe disease ( 94 ). Neutrophils are known to mediate inhibition of NK development, function, and homeostasis ( 95 ) while also being influenced by MAIT population levels, for a controlled immune response ( 76 , 96 ), suggestive of similar roles for LDNs. Unlike other viral infections, we observed no significant changes to majority of the CD4T/CD8T milieu; however, there is evidence for functional exhaustion.…”

Mucosal-Associated Invariant T Cells as a Possible Target to Suppress Secondary Infections at COVID-19

“…We must also point out some arguments that contradict our idea. Thus, neutrophils that are recruited early to sites of infections, including COVID-19 infection, can suppress and prevent overactivation of MAIT cells ( 30 ). Since repeated MAIT cells stimulation by cytokines (IL-12 and IL-18) was found to enhance IL-17 production by MAIT cells ( 31 ), the patients may not benefit from the treatment that suppresses MR1-dependent stimulation.…”

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

“…MAIT cell function may be impaired in settings such as chronic infection ( 115 – 117 ) and cancer ( 118 ). Various studies have implicated immune checkpoints ( 116 , 119 , 120 ), cytokines such as IL-10 ( 121 ) and suppression of MAIT cell function by hydrogen peroxide released from neutrophils ( 122 ). Thus, in addition to recognition of MR1-bound antigen, the context of other signals in different setting is important for MAIT cell activation and function.…”