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您的检索式：作者名="Gowrishankar Muthukrishnan"
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| 1 | Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”显示文摘Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure. | Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley Brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan | 2019 | Bone Research2019，7，3： | 19 |
| 2 | Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation显示文摘Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial,and its role in patients with S.aureus osteomyelitis is unknown.To address this knowledge gap,we completed a clinical study and observed elevated serum IL-27 levels(20-fold higher,P<0.05)in patients compared with healthy controls.Remarkably,IL-27 serum levels were 60-fold higher in patients immediately following septic death than in uninfected patients(P<0.05),suggesting a pathogenic role of IL-27.To test this hypothesis,we evaluated S.aureus osteomyelitis in WT and IL-27Rα^(−/−)mice with and without exogenous IL27 induction by intramuscular injection of rAAV-IL-27p28 or rAAV-GFP,respectively.We found that IL-27 was induced at the surgical site within 1 day of S.aureus infection of bone and was expressed by M0,M1 and M2 macrophages and osteoblasts but not by osteoclasts.Unexpectedly,exogenous IL-27p28(~2 ng·mL^(−1) in serum)delivery ameliorated soft tissue abscesses and periimplant bone loss during infection,accompanied by enhanced local IL-27 expression,significant accumulation of RORγt^(+)neutrophils at the infection site,a decrease in RANK^(+) cells,and compromised osteoclast formation.These effects were not observed in IL-27Rα^(−/−)mice compared with WT mice,suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during infection.In vitro studies and bulk RNA-seq of infected tibiae showed that IL-27 increased nos1,nos2,il17α,il17f,and rorc expression but did not directly stimulate chemotaxis.Collectively,these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following S.aureus infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis. | Yugo Morita Motoo Saito Javier Rangel-Moreno Anthony M.Franchini John R.Owen John C.Martinez John L.Daiss Karen L.de Mesy Bentley Stephen L.Kates Edward M.Schwarz Gowrishankar Muthukrishnan | 2022 | Bone Research2022，10，4： | 0 |
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