Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection.


:Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. Additionally, CXCL4 deficiency decreased leukocyte accumulation in the infected lung with markedly decreased neutrophil infiltration into the lung during early infection and extensive leukocyte, especially lymphocyte accumulation at the late infection stage. Loss of CXCL4 did not affect the activation of adaptive immune T and B lymphocytes during the late stage of lung infection. Further study revealed that CXCL4 deficiency inhibited neutrophil recruitment to the infected mouse lung. Thus the above results identify CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung.


Mucosal Immunol


Mucosal immunology


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




Has Abstract


2017-11-01 00:00:00














  • An African perspective on mucosal immunity and HIV-1.

    abstract::HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune ev...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Pala P,Gomez-Roman VR,Gilmour J,Kaleebu P

    更新日期:2009-07-01 00:00:00

  • Th17-cell plasticity in Helicobacter hepaticus-induced intestinal inflammation.

    abstract::Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is associated with CD4(+) T helper type 1 (Th1) and Th17 responses. However, the relative contributions of these subsets during the induction and resolution of colitis in T-cell-sufficient hosts remain unknown. We report that H...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Morrison PJ,Bending D,Fouser LA,Wright JF,Stockinger B,Cooke A,Kullberg MC

    更新日期:2013-11-01 00:00:00

  • Flagellin: key target of mucosal innate immunity.

    abstract::The mucosal immune system is charged with defending the host's vast interfaces with the outside world from the enormous and diverse group of microbes that colonizes these surfaces. A key means by which the mucosal immune system protects the host from such diverse microbes is using germ-line-encoded receptors that targ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Vijay-Kumar M,Gewirtz AT

    更新日期:2009-05-01 00:00:00

  • The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice.

    abstract::Women with asymptomatic Neisseria gonorrhoeae infection are at risk of developing pelvic inflammatory disease (PID) if the bacteria ascend from the endocervix into the uterus and oviducts. Factors that affect disease severity, ranging from mild discomfort to severe inflammation, pain, and infertility, remain elusive. ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Islam EA,Shaik-Dasthagirisaheb Y,Kaushic C,Wetzler LM,Gray-Owen SD

    更新日期:2016-07-01 00:00:00

  • Architectural and functional alterations of the small intestinal mucosa in classical Whipple's disease.

    abstract::Classical Whipple's disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Epple HJ,Friebel J,Moos V,Troeger H,Krug SM,Allers K,Schinnerling K,Fromm A,Siegmund B,Fromm M,Schulzke JD,Schneider T

    更新日期:2017-11-01 00:00:00

  • Lung niches for the generation and maintenance of tissue-resident memory T cells.

    abstract::The extent to which tissue-specific viral infections generate memory T cells specifically adapted to and maintained within the target infection site is unknown. Here, we show that respiratory virus-specific memory T cells in mice and humans are generated and maintained in compartmentalized niches in lungs, distinct fr...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Turner DL,Bickham KL,Thome JJ,Kim CY,D'Ovidio F,Wherry EJ,Farber DL

    更新日期:2014-05-01 00:00:00

  • Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica.

    abstract::Leptin is an adipocytokine that links nutrition to immunity. Previous observation that a genetic polymorphism in the leptin receptor affected susceptibility to Entamoeba histolytica infection led to the hypothesis that leptin signaling has a protective role during intestinal amebic infection. In this study we show tha...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Guo X,Roberts MR,Becker SM,Podd B,Zhang Y,Chua SC Jr,Myers MG Jr,Duggal P,Houpt ER,Petri WA Jr

    更新日期:2011-05-01 00:00:00

  • MyD88 dependence of beryllium-induced dendritic cell trafficking and CD4⁺ T-cell priming.

    abstract::Beryllium exposure results in beryllium hypersensitivity in a subset of exposed individuals, leading to granulomatous inflammation and fibrosis in the lung. In addition to its antigenic properties, beryllium has potent adjuvant activity that contributes to sensitization via unknown pathways. Here we show that berylliu...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: McKee AS,Mack DG,Crawford F,Fontenot AP

    更新日期:2015-11-01 00:00:00

  • Thymic stromal lymphopoietin (TSLP)-mediated dermal inflammation aggravates experimental asthma.

    abstract::Individuals with one atopic disease are far more likely to develop a second. Approximately half of all atopic dermatitis (AD) patients subsequently develop asthma, particularly those with severe AD. This association, suggesting a role for AD as an entry point for subsequent allergic disease, is a phenomenon known as t...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Han H,Xu W,Headley MB,Jessup HK,Lee KS,Omori M,Comeau MR,Marshak-Rothstein A,Ziegler SF

    更新日期:2012-05-01 00:00:00

  • Cell-secreted Gp96-Ig-peptide complexes induce lamina propria and intraepithelial CD8+ cytotoxic T lymphocytes in the intestinal mucosa.

    abstract::Induction of mucosal immunity is critical for protection from enteric pathogens. Heat shock protein gp96 is one of the primary peptide and protein chaperones located in the endoplasmic reticulum. We reported previously that a cell-secreted gp96-Ig fusion protein (gp96-Ig) mediated strong systemic, antigen-specific CD8...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Strbo N,Pahwa S,Kolber MA,Gonzalez L,Fisher E,Podack ER

    更新日期:2010-03-01 00:00:00

  • Macrophages are critical to the maintenance of IL-13-dependent lung inflammation and fibrosis.

    abstract::The roles of macrophages in type 2-driven inflammation and fibrosis remain unclear. Here, using CD11b-diphtheria toxin receptor (DTR) transgenic mice and three models of interleukin 13 (IL-13)-dependent inflammation, fibrosis, and immunity, we show that CD11b(+) F4/80(+) Ly6C(+) macrophages are required for the mainte...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Borthwick LA,Barron L,Hart KM,Vannella KM,Thompson RW,Oland S,Cheever A,Sciurba J,Ramalingam TR,Fisher AJ,Wynn TA

    更新日期:2016-01-01 00:00:00

  • Joint expedition: linking gut inflammation to arthritis.

    abstract::The tight connection between intestinal inflammation and arthritis in spondyloarthritis (SpA) has been studied extensively. Subclinical gut inflammation, which can be considered as a model for early Crohn's disease, was shown to be strongly associated with joint inflammation. Several early mucosal abnormalities were u...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Jacques P,Elewaut D

    更新日期:2008-09-01 00:00:00

  • Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection.

    abstract::The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Ren W,Liao Y,Ding X,Jiang Y,Yan J,Xia Y,Tan B,Lin Z,Duan J,Jia X,Yang G,Deng J,Zhu C,Hardwidge PR,Li J,Zhu G,Yin Y

    更新日期:2019-03-01 00:00:00

  • Epithelial-mesenchymal transition in Crohn's disease.

    abstract::Crohn's disease (CD) is often accompanied by the complications of intestinal strictures and fistulas. These complications remain obstacles in CD treatment. In recent years, the importance of epithelial-mesenchymal transition in the pathogenesis of CD-associated fistulas and intestinal fibrosis has become apparent. Epi...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Jiang H,Shen J,Ran Z

    更新日期:2018-03-01 00:00:00

  • Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings.

    abstract::Rotaviruses (RV) are the leading cause of gastroenteritis in infants and children worldwide and are associated with high mortality predominately in low-income settings. The virus is classified into G and P serotypes and further into P genotypes based on differences in the surface-exposed proteins VP7 and VP4, respecti...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Clarke E,Desselberger U

    更新日期:2015-01-01 00:00:00

  • Differential effect of vitamin D on NOD2- and TLR-induced cytokines in Crohn's disease.

    abstract::Accumulating evidence implicates defective innate immunity in the pathogenesis of Crohn's disease (CD). Ineffectual NOD2 (nucleotide-binding oligomerization domain 2) is the most common susceptibility gene contributing to CD. Vitamin D (vD), a potent modulator of innate and adaptive immunity, induces NOD2 gene express...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Dionne S,Calderon MR,White JH,Memari B,Elimrani I,Adelson B,Piccirillo C,Seidman EG

    更新日期:2014-11-01 00:00:00

  • Alpha-galactosylceramide enhances mucosal immunity to oral whole-cell cholera vaccines.

    abstract::Cholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae (V. cholerae) that results in 3-4 million cases globally with 100,000-150,000 deaths reported annually. Mostly confined to developing nations, current strategies to control the spread of cholera include the provision of safe drinking water a...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Davitt CJH,Longet S,Albutti A,Aversa V,Nordqvist S,Hackett B,McEntee CP,Rosa M,Coulter IS,Lebens M,Tobias J,Holmgren J,Lavelle EC

    更新日期:2019-07-01 00:00:00

  • Cesarean section increases sensitivity to oxazolone-induced colitis in C57BL/6 mice.

    abstract::Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS a...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Zachariassen LF,Hansen AK,Krych L,Nielsen DS,Holm TL,Tougaard P,Hansen CHF

    更新日期:2019-11-01 00:00:00

  • Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation.

    abstract::How the immune system senses aeroallergens and triggers an aberrant inflammation is poorly understood. Dectin-2 is a house dust mite (HDM)-sensing pattern recognition receptor. In a 3-week mouse model of repeated intranasal HDM challenge, anti-Dectin-2 potently attenuated the characteristic allergic inflammation and a...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Clarke DL,Davis NH,Campion CL,Foster ML,Heasman SC,Lewis AR,Anderson IK,Corkill DJ,Sleeman MA,May RD,Robinson MJ

    更新日期:2014-05-01 00:00:00

  • Noxa/HSP27 complex delays degradation of ubiquitylated IkBα in airway epithelial cells to reduce pulmonary inflammation.

    abstract::IFN-γ is known as a pro-inflammatory cytokine, but can also block inflammation in certain chronic diseases although the underlying mechanisms are poorly understood. We found that IFN-γ rapidly induced Noxa expression and that extent of inflammation by repeated house dust mite exposure was enhanced in noxa-/- compared ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Zhang C,Jones JT,Chand HS,Wathelet MG,Evans CM,Dickey B,Xiang J,Mebratu YA,Tesfaigzi Y

    更新日期:2018-05-01 00:00:00

  • IL-22-binding protein exacerbates influenza, bacterial super-infection.

    abstract::Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptide...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Abood RN,McHugh KJ,Rich HE,Ortiz MA,Tobin JM,Ramanan K,Robinson KM,Bomberger JM,Kolls JK,Manni ML,Pociask DA,Alcorn JF

    更新日期:2019-09-01 00:00:00

  • Oral-gut connection: one step closer to an integrated view of the gastrointestinal tract?

    abstract::Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.1 from Kenya Honda's laboratory show that a subset of orally de...

    journal_title:Mucosal immunology

    pub_type: 评论,杂志文章


    authors: Lira-Junior R,Boström EA

    更新日期:2018-03-01 00:00:00

  • The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.

    abstract::Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV-negative MSM. Here, we...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Kelley CF,Kraft CS,de Man TJ,Duphare C,Lee HW,Yang J,Easley KA,Tharp GK,Mulligan MJ,Sullivan PS,Bosinger SE,Amara RR

    更新日期:2017-07-01 00:00:00

  • Molecular mechanisms regulating TGF-beta-induced Foxp3 expression.

    abstract::Molecular mechanisms regulating transforming growth factor-beta (TGF-beta) induction of Foxp3 (forkhead box P3) expression and thus induction of induced regulatory T cells (Tregs) have been the focus of a great deal of study in recent years. It has become clear that this process is influenced by a number of factors as...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Xu L,Kitani A,Strober W

    更新日期:2010-05-01 00:00:00

  • Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis.

    abstract::Celiac disease is a multifactorial disorder and provides a privileged model to decipher how the interplay between environmental and genetic factors can alter mucosal tolerance to a food antigen, lead to chronic intestinal inflammation, and ultimately promote T-cell lymphomagenesis. Here we summarize how HLA-DQ2/8 mole...

    journal_title:Mucosal immunology

    pub_type: 评论,杂志文章,评审


    authors: Meresse B,Ripoche J,Heyman M,Cerf-Bensussan N

    更新日期:2009-01-01 00:00:00

  • IL-17-mediated antifungal defense in the oral mucosa is independent of neutrophils.

    abstract::Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Trautwein-Weidner K,Gladiator A,Nur S,Diethelm P,LeibundGut-Landmann S

    更新日期:2015-03-01 00:00:00

  • Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization.

    abstract::The generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cell...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: O'Hara JM,Redhu NS,Cheung E,Robertson NG,Patik I,Sayed SE,Thompson CM,Herd M,Lucas KB,Conaway E,Morton CC,Farber DL,Malley R,Horwitz BH

    更新日期:2020-01-01 00:00:00

  • The emergence of pathogenic TNF/iNOS producing dendritic cells (Tip-DCs) in a malaria model of acute respiratory distress syndrome (ARDS) is dependent on CCR4.

    abstract::Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ARDS/ALI is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 (PbN)-induced ...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Galvão-Filho B,de Castro JT,Figueiredo MM,Rosmaninho CG,Antonelli LRDV,Gazzinelli RT

    更新日期:2019-03-01 00:00:00

  • A screen of Crohn's disease-associated microbial metabolites identifies ascorbate as a novel metabolic inhibitor of activated human T cells.

    abstract::Microbial metabolites are an emerging class of mediators influencing CD4+ T-cell function. To advance the understanding of direct causal microbial factors contributing to Crohn's disease, we screened 139 predicted Crohn's disease-associated microbial metabolites for their bioactivity on human CD4+ T-cell functions ind...

    journal_title:Mucosal immunology

    pub_type: 杂志文章


    authors: Chang YL,Rossetti M,Vlamakis H,Casero D,Sunga G,Harre N,Miller S,Humphries R,Stappenbeck T,Simpson KW,Sartor RB,Wu G,Lewis J,Bushman F,McGovern DPB,Salzman N,Borneman J,Xavier R,Huttenhower C,Braun J

    更新日期:2019-03-01 00:00:00

  • The emerging roles of eosinophils in mucosal homeostasis.

    abstract::Eosinophils are granulocytes, typically implicated as end-stage effector cells in type-II immune responses. They are capable of producing a wide array of pre-formed molecules which render them with vast potential to influence a wide variety of processes. Nonetheless, eosinophil research has traditionally focused on th...

    journal_title:Mucosal immunology

    pub_type: 杂志文章,评审


    authors: Shah K,Ignacio A,McCoy KD,Harris NL

    更新日期:2020-07-01 00:00:00