biostudies-literatureLim KU.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of HealthNIAID NIH HHSU.S. Department of Health & Human Services | National Institutes of Health1046-1057https://www.ebi.ac.uk/biostudies/studies/S-EPMC7791396biostudies-literatureUnknown21(9)Early recruitment of neutrophils from the blood to sites of tissue infection is a hallmark of innate immune responses. However, little is known about the mechanisms by which apoptotic neutrophils are cleared in infected tissues during resolution and the immunological consequences of in situ efferocytosis. Using intravital multiphoton microscopy, we show previously unrecognized motility patterns of interactions between neutrophils and tissue-resident phagocytes within the influenza-infected mouse airway. Newly infiltrated inflammatory monocytes become a chief pool of phagocytes and play a key role in the clearance of highly motile apoptotic neutrophils during the resolution phase. Apoptotic neutrophils further release epidermal growth factor and promote the differentiation of monocytes into tissue-resident antigen-presenting cells for activation of antiviral T cell effector functions. Collectively, these results suggest that the presence of in situ neutrophil resolution at the infected tissue is critical for optimal CD8⁺ T cell-mediated immune protection.Nature immunologyIn situ neutrophil efferocytosis shapes T cell immunity to influenza infection.PMC7791396R21 AI149775R21 AI143182T32 AI007285P01 AI102851R01 AI070826F32 AI138415T32 AI118689R01 AI147362Kim THFowell DJTrzeciak ATopham DJAmitrano AMLim KPrizant HReilly ECKim MfalseIn situ neutrophil efferocytosis shapes T cell immunity to influenza infection.Early recruitment of neutrophils from the blood to sites of tissue infection is a hallmark of innate immune responses. However, little is known about the mechanisms by which apoptotic neutrophils are cleared in infected tissues during resolution and the immunological consequences of in situ efferocytosis. Using intravital multiphoton microscopy, we show previously unrecognized motility patterns of interactions between neutrophils and tissue-resident phagocytes within the influenza-infected mouse airway. Newly infiltrated inflammatory monocytes become a chief pool of phagocytes and play a key role in the clearance of highly motile apoptotic neutrophils during the resolution phase. Apoptotic neutrophils further release epidermal growth factor and promote the differentiation of monocytes into tissue-resident antigen-presenting cells for activation of antiviral T cell effector functions. Collectively, these results suggest that the presence of in situ neutrophil resolution at the infected tissue is critical for optimal CD8⁺ T cell-mediated immune protection.2020-01-01T00:00:00Z2020 Sep2024-11-07T03:56:08.543Z2021-02-20T20:45:19ZS-EPMC77913963274781810.1038/s41590-020-0746-x