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IFN-? induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense.

ABSTRACT: The role of interleukin-17A (IL-17A) in host defense against Legionella pneumophila remains elusive. To address this issue, we used Il17a(-/-), Il17f(-/-), and Il17a/Il17f(-/-) mice on a C57Bl/6 (non-permissive) background and IL-17 neutralizing Abs in mice on an A/J (permissive) background. Higher bacterial (L. pneumophila) counts in the lung and blood along with reduced neutrophil recruitment were detected in Il17a(-/-), but not Il17f(-/-), mice. We found that neutrophils produce IL-17A homodimer (IL-17A) during L. pneumophila infection, and hematopoietic cell-derived IL-17A is known to be important for bacterial clearance. Thus, intratracheal administration of wild-type neutrophils or recombinant IL-17A restored bacterial clearance and neutrophil recruitment in Il17a(-/-) mice. Furthermore, neutrophil-depleted Rag2(-/-) and Rag2/Il-2r?(-/-) mice exhibited increased bacterial burden, reduced neutrophil influx and IL-17A production in the lung. Recombinant IFN-? administration in Il17a(-/-) mice augmented bacterial elimination, whereas IL-17A administration in Ifn?(-/-) mice did not augment bacterial clearance. IFN-? is produced by T cells, but not neutrophils or macrophages, suggesting that neutrophil-derived IL-17A induces IFN-? in a paracrine fashion. Human pneumonic lungs and human neutrophils challenged with L. pneumophila exhibited increased numbers of IL-17A producing cells. These findings display a novel function of neutrophil-derived IL-17A in antibacterial defense via the induction of IFN-? in a paracrine manner.

SUBMITTER: Cai S

PROVIDER: S-EPMC4785101 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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IFN-γ induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense.

Cai S S Batra S S Langohr I I Iwakura Y Y Jeyaseelan S S

Mucosal immunology 20150909 3

The role of interleukin-17A (IL-17A) in host defense against Legionella pneumophila remains elusive. To address this issue, we used Il17a(-/-), Il17f(-/-), and Il17a/Il17f(-/-) mice on a C57Bl/6 (non-permissive) background and IL-17 neutralizing Abs in mice on an A/J (permissive) background. Higher bacterial (L. pneumophila) counts in the lung and blood along with reduced neutrophil recruitment were detected in Il17a(-/-), but not Il17f(-/-), mice. We found that neutrophils produce IL-17A homodi ...[more]

PMID: 26349661

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Dataset Information

IFN-? induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense.

Publications

IFN-γ induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense.

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