Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus

Kristina A. Stoermer, Adam Burrack, Lauren Oko, Stephanie A. Montgomery, Luke B. Borst, Ronald G. Gill, Thomas E. Morrison

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Chikungunya virus (CHIKV) and Ross River virus (RRV) cause a debilitating, and often chronic, musculoskeletal inflammatory disease in humans. Macrophages constitute the major inflammatory infiltrates in musculoskeletal tissues during these infections. However, the precise macrophage effector functions that affect the pathogenesis of arthritogenic alphaviruses have not been defined. We hypothesized that the severe damage to musculoskeletal tissues observed in RRV- or CHIKV-infected mice would promote a wound-healing response characterized by M2-like macrophages. Indeed, we found that RRV- and CHIKV-induced musculoskeletal inflammatory lesions, and macrophages present in these lesions, have a unique gene-expression pattern characterized by high expression of arginase 1 and Ym1/Chi3l3 in the absence of FIZZ1/Relmα that is consistent with an M2-like activation phenotype. Strikingly, mice specifically deleted for arginase 1 in neutrophils and macrophages had dramatically reduced viral loads and improved pathology in musculoskeletal tissues at late times post-RRV infection. These findings indicate that arthritogenic alphavirus infection drives a unique myeloid cell activation program in inflamed musculoskeletal tissues that inhibits virus clearance and impedes disease resolution in an arginase 1-dependent manner.

Original languageEnglish (US)
Pages (from-to)4047-4059
Number of pages13
JournalJournal of Immunology
Volume189
Issue number8
DOIs
StatePublished - Oct 15 2012

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Alphavirus
Ross River virus
Arginase
Chikungunya virus
Neutrophils
Macrophages
Alphavirus Infections
Musculoskeletal Diseases
Virus Diseases
Myeloid Cells
Viral Load
Wound Healing
Pathology
Viruses
Phenotype
Gene Expression
Infection

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Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus. / Stoermer, Kristina A.; Burrack, Adam; Oko, Lauren; Montgomery, Stephanie A.; Borst, Luke B.; Gill, Ronald G.; Morrison, Thomas E.

In: Journal of Immunology, Vol. 189, No. 8, 15.10.2012, p. 4047-4059.

Research output: Contribution to journalArticle

Stoermer, Kristina A. ; Burrack, Adam ; Oko, Lauren ; Montgomery, Stephanie A. ; Borst, Luke B. ; Gill, Ronald G. ; Morrison, Thomas E. / Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus. In: Journal of Immunology. 2012 ; Vol. 189, No. 8. pp. 4047-4059.
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