PuSH - Publication Server of Helmholtz Zentrum München: Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

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Shi, R.* ; Cao, Z.* ; Li, H.* ; Graw, J. ; Zhang, G.* ; Thannickal, V.J.* ; Cheng, G.*

Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

PLoS Pathog. 14:e1007026 (2018)

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Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

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