دورية أكاديمية
Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.
| العنوان: | Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease. |
|---|---|
| المؤلفون: | Santos FM; Department of Morphology, Drug Research and Development Center, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Costa VRdM; Department of Morphology, Drug Research and Development Center, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Araújo Sd; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Sousa CDFd; Department of Microbiology, Host Microorganism Interaction Laboratory, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Moreira TP; Department of Microbiology, Host Microorganism Interaction Laboratory, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Gonçalves MR; Department of Morphology, Drug Research and Development Center, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Santos ACPMd; Department of Microbiology, Host Microorganism Interaction Laboratory, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Ferreira HAS; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Costa PAC; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Barrioni BR; Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Bargi-Souza P; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Pereira MdM; Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Nogueira ML; Virology Research Laboratory, São José do Rio Preto School of Medicine (FAMERP), São José do Rio Preto, São Paulo, Brazil., Souza DdG; Department of Microbiology, Host Microorganism Interaction Laboratory, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Guimarães PPG; Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Teixeira MM; Department of Biochemistry and Immunology, Drug Research and Development Center, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Queiroz-Junior CM; Department of Morphology, Drug Research and Development Center, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Costa VV; Department of Morphology, Drug Research and Development Center, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. |
| المصدر: | Journal of virology [J Virol] 2024 Jan 23; Vol. 98 (1), pp. e0110223. Date of Electronic Publication: 2024 Jan 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Alphavirus Infections*/immunology , Arthritis*/immunology , Arthritis*/virology , Chemokine CCL2*/immunology , Receptors, CCR2*/immunology, Animals ; Mice ; Alphavirus ; Interleukin-6/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Male ; Bone Diseases/virology |
| مستخلص: | Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2 -/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2 + macrophages and a cellular response orchestrated by these cells. CCR2 -/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2 -/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV. Competing Interests: The authors declare no conflict of interest. |
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| معلومات مُعتمدة: | U01 AI151807 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: CCL2 chemokine; CCR2 receptor; Mayaro virus; alphavirus; bone loss; inflammation |
| المشرفين على المادة: | 0 (Chemokine CCL2) 0 (Interleukin-6) 0 (Receptors, CCR2) 0 (Ccl2 protein, mouse) 0 (Ccr2 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240103 Date Completed: 20240215 Latest Revision: 20240704 |
| رمز التحديث: | 20240704 |
| مُعرف محوري في PubMed: | PMC10805060 |
| DOI: | 10.1128/jvi.01102-23 |
| PMID: | 38169294 |
| قاعدة البيانات: | MEDLINE |
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