• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2018
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2018
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

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

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Ford, J.
    Hughson, A.
    Lim, K.
    Date
    2018
    Journal
    Frontiers in immunology
    Publisher
    Frontiers Media
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.3389/fimmu.2018.03063
    Abstract
    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 Leishmania major infection, CCL7 is specifically upregulated in the skin one-2 weeks after infection but its role in L. major control is unclear. To determine CCL7's impact on the response to L. major we infected WT and CCL7-/- C57BL/6 mice. L. major infection of CCL7-deficient mice led to an unexpected increase 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 in vitro and CCL7 add-back in vivo specifically reduced neutrophil influx into the infected skin revealing an unexpected role for CCL7 in limiting neutrophil recruitment during L. major infection. Enhanced neutrophilic infiltration in CCL7-deficient mice changed the balance of L. major infected host cells with an increase in the ratio of infected neutrophils over monocytes/macrophages. To determine the consequence of CCL7 deficiency on L. major 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 L. major 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.
    Keyword
    CCL7
    chemokine
    inflammation
    Leishmania major
    macrophage
    neutrophils
    parasite
    skin
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060388412&doi=10.3389%2ffimmu.2018.03063&partnerID=40&md5=0ef7964aceaa003981c85db237af5370; http://hdl.handle.net/10713/9383
    ae974a485f413a2113503eed53cd6c53
    10.3389/fimmu.2018.03063
    Scopus Count
    Collections
    UMB Open Access Articles 2018

    entitlement

    Related articles

    • CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation.
    • Authors: Sato N, Ahuja SK, Quinones M, Kostecki V, Reddick RL, Melby PC, Kuziel WA, Ahuja SS
    • Issue date: 2000 Jul 17
    • The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice.
    • Authors: Charmoy M, Hurrell BP, Romano A, Lee SH, Ribeiro-Gomes F, Riteau N, Mayer-Barber K, Tacchini-Cottier F, Sacks DL
    • Issue date: 2016 Apr
    • Transgenic expression of CXCR3 on T cells enhances susceptibility to cutaneous Leishmania major infection by inhibiting monocyte maturation and promoting a Th2 response.
    • Authors: Oghumu S, Stock JC, Varikuti S, Dong R, Terrazas C, Edwards JA, Rappleye CA, Holovatyk A, Sharpe A, Satoskar AR
    • Issue date: 2015 Jan
    • CC chemokine receptor 1 enhances susceptibility to Leishmania major during early phase of infection.
    • Authors: Rodriguez-Sosa M, Rosas LE, Terrazas LI, Lu B, Gerard C, Satoskar AR
    • Issue date: 2003 Apr
    • Galectin-3 facilitates neutrophil recruitment as an innate immune response to a parasitic protozoa cutaneous infection.
    • Authors: Bhaumik P, St-Pierre G, Milot V, St-Pierre C, Sato S
    • Issue date: 2013 Jan 15
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.