Abstract
Neutrophil recruitment to the site of injury is an essential first step of an anti-bacterial response. However, little is known about the basis for and relevance of neutrophil migration from inflamed tissue into lymphoid organs. We established a photoconversion-based system to monitor the fate of neutrophils recruited to inflamed skin. While neutrophils are efficiently recruited to sites of both microbial and sterile lesions, subsequent re-localization to draining lymph nodes happens only when bacteria are present in the primary lesion. Skin egress of neutrophils occurs via lymphatic vessels and is dependent on CD11b and CXCR4 but not CCR7. Neutrophils are the predominant immune cell to migrate from inflamed skin into lymph nodes where they augment lymphocyte proliferation. Furthermore, inhibition of neutrophil migration from skin reduces T-cell proliferation in draining lymph nodes. Thus neutrophils mediate rapid cellular communication between the initial injury site and secondary lymphoid organs and modulate immune responsiveness.
Highlights
Neutrophil recruitment to the site of injury is an essential first step of an anti-bacterial response
CD11b was preferentially expressed on neutrophils recruited in response to S. aureus, while CD62L and CXCR2 were higher on neutrophils responding to sterile injury (Fig. 1b)
Since blocking CXCR4 reduced neutrophil migration from skin to draining lymph nodes, we expect that inhibition of CXCR4 would lead to a similar decrease in T-cell proliferation in draining lymph nodes and would provide additional opportunities for modulating adaptive immune responses via regulation of lymphatic migration of neutrophils. These data suggest that the rapid dissemination of neutrophils from the site of bacterial inflammation to secondary lymphoid organs may enhance lymphocyte responses, thereby providing an additional link between the innate and adaptive immune systems. In addition to their well-known role in pathogen killing in inflamed tissues, recent evidence indicates that neutrophils may affect adaptive immune responses in lymphoid organs[2]
Summary
Neutrophil recruitment to the site of injury is an essential first step of an anti-bacterial response. While neutrophils are efficiently recruited to sites of both microbial and sterile lesions, subsequent re-localization to draining lymph nodes happens only when bacteria are present in the primary lesion. Neutrophils are the predominant immune cell to migrate from inflamed skin into lymph nodes where they augment lymphocyte proliferation. While neutrophils entered inflamed skin in response to both bacterial and sterile injuries, migration to draining lymph nodes was dependent on the presence of bacteria. Neutrophil persistence in the lymph nodes was reduced in comparison to inflamed skin, we found that skinegressing neutrophils were able to augment lymphocyte proliferation in draining lymph nodes These data indicate a previously unappreciated level of communication between pathogens and neutrophils that promotes lymphatic migration of neutrophils and modulates downstream immune responses
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