Editors' ChoiceIMMUNITY

The Neutrophil: A Work Horse, Not a Trojan Horse

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Science Translational Medicine  21 Nov 2012:
Vol. 4, Issue 161, pp. 161ec213
DOI: 10.1126/scitranslmed.3005329

Devious intracellular pathogens can use neutrophils as a carrying vessel, quietly slipping past the host defense, much like the Greeks and the mythological Trojan horse. However, new research now demonstrates that the neutrophil goes above and beyond its regular defensive duties to knowingly capture tissue antigens and carry them back to the bone marrow in order to stimulate adaptive CD8+ T lymphocyte immunity.

Duffy et al. established an intradermal immunization protocol in mice using a modified vaccinia virus. They found that although an expected number of CD8+ and CD4+ T cells proliferated in the draining lymph nodes, a large portion of CD8+ T cell also demonstrated polyclonal priming within the bone marrow. These CD8+ T cells did not migrate to the bone marrow from draining lymph nodes, as a chemical inhibitor of lymphocyte egress from the nodes had no effect on marrow proliferation. Instead, to understand how antigen reached the marrow, the authors injected intradermal fluorescently labeled vaccinia antigen and followed its uptake. Neutrophils rapidly infiltrated the intradermal site and engulfed the antigen. Surprisingly, some of these neutrophils trafficked back to the bone marrow through the blood. Depleting neutrophils, or impairing their migration, abolished the bone marrow CD8+ T cell response; however, the draining CD8+ T cell lymph node response was unaffected. Intradermal injection of purified neutrophils loaded with virus antigen also homed to the bone marrow using the chemokine receptor CXCR4. Interestingly, the neutrophil did not directly present the antigen; instead, an intermediary marrow myeloid cell was required. The bone marrow CD8+ T cells were phenotypically distinct from draining lymph node–stimulated CD8+ T cells, each demonstrating individual patterns of cytokine and gene expression and cytotoxic capacity. Therefore, neutrophils are critical for establishing an alternative and unique marrow-dependent CD8+ T cell response.

Classically, the bone marrow is thought of as the site of hematopoesis and as an organ to remove old cells, such as circulating neutrophils. However, this new research demonstrates that the bone marrow is a major site of an alternative adaptive immune response that requires neutrophils to deliver peripheral tissue antigen. This study reveals the importance of neutrophils as a key component of the adaptive immune system and highlights their consideration for future vaccine development strategies

D. Duffy et al., Neutrophils transport antigen from the dermis to the bone marrow, initiating a source of CD8+ T cells. Immunity 37, 1–13 (2012). [Abstract]

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