@article{14f1cd52484f404a8c8388193e8da566,
title = "CCR2 contributes to host defense against Staphylococcus aureus orthopedic implant-associated infections in mice",
abstract = "C-C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant-associated infections (OIAI), but whether CCR2-mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic-grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2-deficient mice. In vivo bioluminescent signals significantly increased in CCR2-deficient mice compared with wt mice at later time points (Days 14–28), which was confirmed with ex vivo colony-forming unit enumeration. S. aureus γ-hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ-hemolysin-deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ-hemolysin virulence. Although CCR2-deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2-deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread.",
author = "Yu Wang and Dustin Dikeman and Jeffrey Zhang and Nicole Ackerman and Sophia Kim and Alphonse, {Martin P.} and Ortines, {Roger V.} and Haiyun Liu and Joyce, {Daniel P.} and Dillen, {Carly A.} and Thompson, {John M.} and Thomas, {Abigail A.} and Plaut, {Roger D.} and Miller, {Lloyd S.} and Archer, {Nathan K.}",
note = "Funding Information: This study was funded in part by grants R01AR073665 (L.S.M. and N.K.A.) and R01AR069502 (L.S.M. and N.K.A.) from the U.S. National Institutes of Health (NIH). Strain NRS384 was obtained through the Network on Antimicrobial Resistance in (NARSA), supported under NIAID, NIH contract no. N01‐AI‐95359. L.S.M. is a full‐time employee of Janssen Pharmaceuticals and owns hold Johnson & Johnson stock. L.S.M. performed all work at his prior affiliation at Johns Hopkins University School of Medicine and he has received prior grant support from AstraZeneca, Pfizer, Boehringer Ingelheim, Regeneron Pharmaceuticals, and Moderna Therapeutics, was a paid consultant for Armirall and Janssen Research and Development, was on the scientific advisory board of Integrated Biotherapeutics and is a shareholder of Noveome Biotherapeutics, which are all developing therapeutics against infections (including and other pathogens) and/or inflammatory conditions. Staphylococcus aureus S. aureus Funding Information: This study was funded in part by grants R01AR073665 (L.S.M. and N.K.A.) and R01AR069502 (L.S.M. and N.K.A.) from the U.S. National Institutes of Health (NIH). Strain NRS384 was obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA), supported under NIAID, NIH contract no. N01-AI-95359. L.S.M. is a full-time employee of Janssen Pharmaceuticals and owns hold Johnson & Johnson stock. L.S.M. performed all work at his prior affiliation at Johns Hopkins University School of Medicine and he has received prior grant support from AstraZeneca, Pfizer, Boehringer Ingelheim, Regeneron Pharmaceuticals, and Moderna Therapeutics, was a paid consultant for Armirall and Janssen Research and Development, was on the scientific advisory board of Integrated Biotherapeutics and is a shareholder of Noveome Biotherapeutics, which are all developing therapeutics against infections (including S. aureus and other pathogens) and/or inflammatory conditions. Publisher Copyright: {\textcopyright} 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC",
year = "2022",
month = feb,
doi = "10.1002/jor.25027",
language = "English (US)",
volume = "40",
pages = "409--419",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "2",
}