Details

Autor(en) / Beteiligte

• Ford, Jill
• Hughson, Angela
• Lim, Kihong
• Bardina, Susana V
• Lu, Wuyuan
• Charo, Israel F
• Lim, Jean K
• Fowell, Deborah J

Titel

CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Leishmania major Infection

Ist Teil von

• Frontiers in immunology, 2019-01, Vol.9, p.3063-3063

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The chemokine CCL7 (MCP3) is known to promote the recruitment of many innate immune cell types including monocytes and neutrophils to sites of bacterial and viral infection and eosinophils and basophils to sites of allergic inflammation. CCL7 upregulation has been associated with many inflammatory settings including infection, cardiovascular disease, and the tumor microenvironment. CCL7's pleotropic effects are due in part to its ability to bind numerous chemokine receptors, namely CCR1, CCR2, CCR3, CCR5, and CCR10. CCL7-blockade or CCL7-deficiency is often marked by decreased inflammation and poor pathogen control. In the context of infection, CCL7 is specifically upregulated in the skin one-2 weeks after infection but its role in control is unclear. To determine CCL7's impact on the response to we infected WT and CCL7 C57BL/6 mice. infection of CCL7-deficient mice led to an unexpected in inflammation in the infected skin 2 weeks post-infection. A broad increase in immune cell subsets was observed but was dominated by enhanced neutrophilic infiltration. Increased neutrophil recruitment was associated with an enhanced IL-17 gene profile in the infected skin. CCL7 was shown to directly antagonize neutrophil migration and CCL7 add-back specifically reduced neutrophil influx into the infected skin revealing an unexpected role for CCL7 in limiting neutrophil recruitment during infection. Enhanced neutrophilic infiltration in CCL7-deficient mice changed the balance of infected host cells with an increase in the ratio of infected neutrophils over monocytes/macrophages. To determine the consequence of CCL7 deficiency on control we analyzed parasite load cutaneously at the site of infection and viscerally in the draining LN and spleen. The CCL7 mice supported robust cutaneous parasite control similar to their WT C57BL/6 counterparts. In contrast, CCL7-deficiency led to greater parasite dissemination and poor parasite control in the spleen. Our studies reveal a novel role for CCL7 in negatively regulating cutaneous inflammation, specifically neutrophils, early during infection. We propose that CCL7-mediated dampening of the early immune response in the skin may limit the ability of the parasite to disseminate without compromising cutaneous control.