CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17.


:Post influenza bacterial pneumonia is associated with significant mortality and morbidity. Dendritic cells (DCs) play a crucial role in host defense against bacterial pneumonia, but their contribution to post influenza-susceptibility to secondary bacterial pneumonia is incompletely understood. WT and CCR2-/- mice were infected with 100 plaque forming units (pfu) H1N1 intranasally alone or were challenged on day 5 with 7 × 107 colony forming units (cfu) methicillin-resistant Staphylococcus aureus intratracheally. WT mice express abundant CCL2 mRNA and protein post-H1N1 alone or dual infection. CCR2-/- mice had significantly higher survival as compared to WT mice, associated with significantly improved bacterial clearance at 24 and 48 h (10-fold and 14-fold, respectively) post bacterial challenge. There was robust upregulation of IL-23 and IL-17 as well as downregulation of IL-27 expression in CCR2-/- mice following sequential infection as compared to WT mice, which was also associated with significantly greater accumulation of CD103+ DC. Finally, WT mice treated with a CCR2 inhibitor showed improved bacterial clearance in association with similar cytokine profiles as CCR2-/- mice. Thus, CCR2 significantly contributes to increased susceptibility to bacterial infection after influenza pneumonia likely via altered dendritic cell responses and thus, CCR2 antagonism represents a potential therapeutic strategy.


Mucosal Immunol


Mucosal immunology


Gurczynski SJ,Nathani N,Warheit-Niemi HI,Hult EM,Podsiad A,Deng J,Zemans RL,Bhan U,Moore BB




Has Abstract


2019-03-01 00:00:00














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    abstract::The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (...

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    authors: Karuppuchamy T,Behrens EH,González-Cabrera P,Sarkisyan G,Gima L,Boyer JD,Bamias G,Jedlicka P,Veny M,Clark D,Peach R,Scott F,Rosen H,Rivera-Nieves J

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    authors: Wahid R,Fresnay S,Levine MM,Sztein MB

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    authors: Bergqvist P,Stensson A,Hazanov L,Holmberg A,Mattsson J,Mehr R,Bemark M,Lycke NY

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    authors: Ráki M,Beitnes AC,Lundin KE,Jahnsen J,Jahnsen FL,Sollid LM

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    authors: Rakoff-Nahoum S,Medzhitov R

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    authors: Dagenais M,Dupaul-Chicoine J,Champagne C,Skeldon A,Morizot A,Saleh M

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    authors: Yamamoto K,Nishiumi S,Yang L,Klimatcheva E,Pandina T,Takahashi S,Matsui H,Nakamura M,Zauderer M,Yoshida M,Azuma T

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    authors: Dudek M,Puttur F,Arnold-Schrauf C,Kühl AA,Holzmann B,Henriques-Normark B,Berod L,Sparwasser T

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    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Lau-Kilby AW,Turfkruyer M,Kehl M,Yang L,Buchholz UJ,Hickey K,Malloy AMW

    更新日期:2020-03-01 00:00:00

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    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Guo L,Feng K,Wang YC,Mei JJ,Ning RT,Zheng HW,Wang JJ,Worthen GS,Wang X,Song J,Li QH,Liu LD

    更新日期:2017-11-01 00:00:00

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    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Alam A,Leoni G,Wentworth CC,Kwal JM,Wu H,Ardita CS,Swanson PA,Lambeth JD,Jones RM,Nusrat A,Neish AS

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    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Clay SL,Bravo-Blas A,Wall DM,MacLeod MKL,Milling SWF

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    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Dillon SM,Lee EJ,Kotter CV,Austin GL,Dong Z,Hecht DK,Gianella S,Siewe B,Smith DM,Landay AL,Robertson CE,Frank DN,Wilson CC

    更新日期:2014-07-01 00:00:00