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The YIN and YANG of lipoproteins in developing and preventing infectious arthritis by Staphylococcus aureus.

Journal article
Authors Majd Mohammad
Minh-Thu Nguyen
Cecilia Engdahl
Manli Na
Anders Jarneborn
Zhicheng Hu
Anna Karlsson
Rille Pullerits
Abukar Ali
Friedrich Götz
Tao Jin
Published in PLoS pathogens
Volume 15
Issue 6
Pages e1007877
ISSN 1553-7374
Publication year 2019
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages e1007877
Language en
Links dx.doi.org/10.1371/journal.ppat.100...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Infectious Medicine, Rheumatology and Autoimmunity

Abstract

Rapid bone destruction often leads to permanent joint dysfunction in patients with septic arthritis, which is mainly caused by Staphylococcus aureus (S. aureus). Staphylococcal cell wall components are known to induce joint inflammation and bone destruction. Here, we show that a single intra-articular injection of S. aureus lipoproteins (Lpps) into mouse knee joints induced chronic destructive macroscopic arthritis through TLR2. Arthritis was characterized by rapid infiltration of neutrophils and monocytes. The arthritogenic effect was mediated mainly by macrophages/monocytes and partially via TNF-α but not by neutrophils. Surprisingly, a S. aureus mutant lacking Lpp diacylglyceryl transferase (lgt) caused more severe joint inflammation, which coincided with higher bacterial loads of the lgt mutant in local joints than those of its parental strain. Coinjection of pathogenic S. aureus LS-1 with staphylococcal Lpps into mouse knee joints caused improved bacterial elimination and diminished bone erosion. The protective effect of the Lpps was mediated by their lipid moiety and was fully dependent on TLR2 and neutrophils. The blocking of CXCR2 on neutrophils resulted in total abrogation of the protective effect of the Lpps. Our data demonstrate that S. aureus Lpps elicit innate immune responses, resulting in a double-edged effect. On the one hand, staphylococcal Lpps boost septic arthritis. On the other hand, Lpps act as adjuvants and activate innate immunity, which could be useful for combating infections with multiple drug-resistant strains.

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