A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection.


:Polymorphisms in the essential autophagy gene Atg16L1 have been linked with susceptibility to Crohn's disease, a major type of inflammatory bowel disease (IBD). Although the inability to control intestinal bacteria is thought to underlie IBD, the role of Atg16L1 during extracellular intestinal bacterial infections has not been sufficiently examined and compared to the function of other IBD susceptibility genes, such as Nod2, which encodes a cytosolic bacterial sensor. We find that Atg16L1 mutant mice are resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. An Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, but this hyperimmune phenotype and its protective effects are lost in Atg16L1/Nod2 double-mutant mice. These results reveal an immunosuppressive function of Atg16L1 and suggest that gene variants affecting the autophagy pathway may have been evolutionarily maintained to protect against certain life-threatening infections.


Cell Host Microbe


Cell host & microbe


Marchiando AM,Ramanan D,Ding Y,Gomez LE,Hubbard-Lucey VM,Maurer K,Wang C,Ziel JW,van Rooijen N,Nuñez G,Finlay BB,Mysorekar IU,Cadwell K




Has Abstract


2013-08-14 00:00:00














  • Innate recognition of cell wall β-glucans drives invariant natural killer T cell responses against fungi.

    abstract::iNKT cells are innate T lymphocytes recognizing endogenous and foreign lipid antigens presented in the MHC-like molecule CD1d. The semi-invariant iNKT cell TCR can detect certain bacterial and parasitic lipids and drive iNKT cell responses. How iNKT cells respond to fungi, however, is unknown. We found that CD1d-defic...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Cohen NR,Tatituri RV,Rivera A,Watts GF,Kim EY,Chiba A,Fuchs BB,Mylonakis E,Besra GS,Levitz SM,Brigl M,Brenner MB

    更新日期:2011-11-17 00:00:00

  • Making It Stick: A Compelling Case for Precision Microbiome Reconstitution.

    abstract::Modification of the intestinal microbiome is an emerging target to improve health and prevent or treat a number of diseases. In this issue of Cell Host & Microbe, Maldonado-Gómez et al. (2016) uncover the basic principles that govern the successful establishment and persistence of an exogenously introduced gut bacteri...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Berry D

    更新日期:2016-10-12 00:00:00

  • Dyeing to learn more about the gut microbiota.

    abstract::The switch from culture-based enumeration to deep sequencing has enabled microbial community composition to be profiled en masse. In a new article, Maurice et al. (2013) report the use of fluorescence-activated cell sorting (FACS) to perform a high-throughput analysis of gut microbiota community function. ...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Donia MS,Fischbach MA

    更新日期:2013-02-13 00:00:00

  • A Sialylated Voltage-Dependent Ca2+ Channel Binds Hemagglutinin and Mediates Influenza A Virus Entry into Mammalian Cells.

    abstract::Influenza A virus (IAV) infection is initiated by the attachment of the viral glycoprotein hemagglutinin (HA) to sialic acid on the host cell surface. However, the sialic acid-containing receptor crucial for IAV infection has remained unidentified. Here, we show that HA binds to the voltage-dependent Ca2+ channel Cav1...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Fujioka Y,Nishide S,Ose T,Suzuki T,Kato I,Fukuhara H,Fujioka M,Horiuchi K,Satoh AO,Nepal P,Kashiwagi S,Wang J,Horiguchi M,Sato Y,Paudel S,Nanbo A,Miyazaki T,Hasegawa H,Maenaka K,Ohba Y

    更新日期:2018-06-13 00:00:00

  • Pathogens' exploitation of the intestinal food web.

    abstract::Competition for nutrients is a key factor controlling pathogen colonization within the gastrointestinal tract. In this issue, Ferreyra et al. (2014) and Curtis et al. (2014) show that diverse enteric pathogens can exploit a metabolic byproduct from the commensal microbiota, succinate, to enhance their own virulence ex...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Pham N TA,Lawley TD

    更新日期:2014-12-10 00:00:00

  • A new antituberculosis drug that selectively kills nonmultiplying Mycobacterium tuberculosis.

    abstract::An important report by Bryk et al. in this issue of Cell Host & Microbe describes the properties of a rhodanine prodrug active against nonmultiplying Mycobacterium tuberculosis (Mtb). Considering the tolerance of nonreplicating Mtb to most currently available agents, such a drug could be a major addition to our antitu...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Mitchison DA

    更新日期:2008-03-13 00:00:00

  • Surviving as a Community: Antibiotic Tolerance and Persistence in Bacterial Biofilms.

    abstract::Biofilms are surface-associated bacterial communities that play both beneficial and harmful roles in nature, medicine, and industry. Tolerant and persister cells are thought to underlie biofilm-related bacterial recurrence in medical and industrial contexts. Here, we review recent progress aimed at understanding the m...

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: Yan J,Bassler BL

    更新日期:2019-07-10 00:00:00

  • Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium.

    abstract::Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that m...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Zhang S,Lebreton F,Mansfield MJ,Miyashita SI,Zhang J,Schwartzman JA,Tao L,Masuyer G,Martínez-Carranza M,Stenmark P,Gilmore MS,Doxey AC,Dong M

    更新日期:2018-02-14 00:00:00

  • The Impact of the Microbiome on Immunity to Vaccination in Humans.

    abstract::Vaccines are the most effective means available for preventing infectious diseases. However, vaccine-induced immune responses are highly variable between individuals and between populations in different regions of the world. Understanding the basis of this variation is, thus, of fundamental importance to human health....

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: de Jong SE,Olin A,Pulendran B

    更新日期:2020-08-12 00:00:00

  • GM-CSF-facilitated dendritic cell recruitment and survival govern the intestinal mucosal response to a mouse enteric bacterial pathogen.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes dendritic cell (DC) differentiation and survival in vitro. However, its role in host defense at the intestinal mucosa is unknown. We report that infection with the mouse enteric pathogen, Citrobacter rodentium, increased colonic GM-CSF production and C...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Hirata Y,Egea L,Dann SM,Eckmann L,Kagnoff MF

    更新日期:2010-02-18 00:00:00

  • The HIV-1 Tat team gets bigger.

    abstract::Productive transcription of the HIV-1 genome involves RNA polymerase II working in concert with the viral protein Tat and its team of cofactors in a highly orchestrated process. Now, Pagans and colleagues report that the lysine methyltransferase Set7/9-KMT7 associates with Tat to stimulate RNA polymerase II elongation...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Rice AP

    更新日期:2010-03-18 00:00:00

  • Spacer Acquisition Rates Determine the Immunological Diversity of the Type II CRISPR-Cas Immune Response.

    abstract::CRISPR-Cas systems provide acquired immunity in prokaryotes. Upon infection, short sequences from the phage genome, known as spacers, are inserted between the CRISPR repeats. Spacers are transcribed into small RNA molecules that guide nucleases to their targets. The forces that shape the distribution of newly acquired...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Heler R,Wright AV,Vucelja M,Doudna JA,Marraffini LA

    更新日期:2019-02-13 00:00:00

  • A mouse model for the human pathogen Salmonella typhi.

    abstract::Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a life-threatening human disease. The lack of animal models due to S. Typhi's strict human host specificity has hindered its study and vaccine development. We find that immunodeficient Rag2(-/-) γc(-/-) mice engrafted with human fetal liver hematopoiet...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Song J,Willinger T,Rongvaux A,Eynon EE,Stevens S,Manz MG,Flavell RA,Galán JE

    更新日期:2010-10-21 00:00:00

  • Tracking Vibrio cholerae Cell-Cell Interactions during Infection Reveals Bacterial Population Dynamics within Intestinal Microenvironments.

    abstract::Vibrio cholerae is the causative agent of the diarrheal disease cholera. Although many V. cholerae virulence factors have been studied, the role of interbacterial interactions within the host gut and their influence on colonization are poorly understood. Here, we utilized the conjugative properties of a Vibrio-specifi...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Fu Y,Ho BT,Mekalanos JJ

    更新日期:2018-02-14 00:00:00

  • Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice.

    abstract::Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Carvalho FA,Koren O,Goodrich JK,Johansson ME,Nalbantoglu I,Aitken JD,Su Y,Chassaing B,Walters WA,González A,Clemente JC,Cullender TC,Barnich N,Darfeuille-Michaud A,Vijay-Kumar M,Knight R,Ley RE,Gewirtz AT

    更新日期:2012-08-16 00:00:00

  • Phosphoinositides influence pathogen surfing: EPEC rights the SHIP.

    abstract::Tir, a translocated effector protein from enteropathogenic E. coli (EPEC), contains two phosphotyrosines that initiate cellular signaling cascades, leading to localized actin polymerization into pedestals. A recent study now shows that two additional tyrosines within Tir recruit the inositol phosphatase SHIP2 to gener...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Campellone KG

    更新日期:2010-01-21 00:00:00

  • Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein Facilitates Viral Replication.

    abstract::Herpes simplex virus 1 (HSV-1) establishes infections in humans and mice, but some non-human primates exhibit resistance via unknown mechanisms. Innate immune recognition pathways are highly conserved but are pivotal in determining susceptibility to DNA virus infections. We report that variation of a single amino acid...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Zhang J,Zhao J,Xu S,Li J,He S,Zeng Y,Xie L,Xie N,Liu T,Lee K,Seo GJ,Chen L,Stabell AC,Xia Z,Sawyer SL,Jung J,Huang C,Feng P

    更新日期:2018-08-08 00:00:00

  • Programing of an Intravascular Immune Firewall by the Gut Microbiota Protects against Pathogen Dissemination during Infection.

    abstract::Eradication of pathogens from the bloodstream is critical to prevent disseminated infections and sepsis. Kupffer cells in the liver form an intravascular firewall that captures and clears pathogens from the blood. Here, we show that the catching and killing of circulating pathogens by Kupffer cells in vivo are promote...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: McDonald B,Zucoloto AZ,Yu IL,Burkhard R,Brown K,Geuking MB,McCoy KD

    更新日期:2020-11-11 00:00:00

  • Durable protection from Herpes Simplex Virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene.

    abstract::A vaginal microbicide should prevent pathogen transmission without disrupting tissue barriers to infection. Ideally, it would not need to be applied immediately before sexual intercourse, when compliance is a problem. Intravaginal administration of small interfering RNA (siRNA) lipoplexes targeting Herpes Simplex Viru...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Wu Y,Navarro F,Lal A,Basar E,Pandey RK,Manoharan M,Feng Y,Lee SJ,Lieberman J,Palliser D

    更新日期:2009-01-22 00:00:00

  • Cofactors required for TLR7- and TLR9-dependent innate immune responses.

    abstract::Pathogens commonly utilize endocytic pathways to gain cellular access. The endosomal pattern recognition receptors TLR7 and TLR9 detect pathogen-encoded nucleic acids to initiate MyD88-dependent proinflammatory responses to microbial infection. Using genome-wide RNAi screening and integrative systems-based analysis, w...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Chiang CY,Engel A,Opaluch AM,Ramos I,Maestre AM,Secundino I,De Jesus PD,Nguyen QT,Welch G,Bonamy GM,Miraglia LJ,Orth AP,Nizet V,Fernandez-Sesma A,Zhou Y,Barton GM,Chanda SK

    更新日期:2012-03-15 00:00:00

  • Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation.

    abstract::Hepatitis C virus (HCV) is a single-stranded RNA virus encoding a single polyprotein whose translation is driven by an internal ribosome entry site (IRES). HCV infection strongly induces antiviral interferon-stimulated gene (ISG) expression in the liver, yet it persists, suggesting that HCV can block ISG effector func...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Garaigorta U,Chisari FV

    更新日期:2009-12-17 00:00:00

  • Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria.

    abstract::Cerebral malaria is a complication of Plasmodium falciparum infection characterized by sudden coma, death, or neurodisability. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that blood-brain barrier disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal m...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Zhao H,Aoshi T,Kawai S,Mori Y,Konishi A,Ozkan M,Fujita Y,Haseda Y,Shimizu M,Kohyama M,Kobiyama K,Eto K,Nabekura J,Horii T,Ishino T,Yuda M,Hemmi H,Kaisho T,Akira S,Kinoshita M,Tohyama K,Yoshioka Y,Ishii KJ,Co

    更新日期:2014-05-14 00:00:00

  • Enteric infection and inflammation alter gut microbial ecology.

    abstract::The complex microbial community residing within the intestine plays important roles in host defense. However, the impact of enteric infection and inflammation on this resident community has not been fully explored. In this issue of Cell Host & Microbe, Lupp and coworkers reveal that the composition of the intestinal m...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Rawls JF

    更新日期:2007-08-16 00:00:00

  • Bacterial persistence: finding the "sweet spot".

    abstract::Studies described by Eisele et al. (2013) and Xavier et al. (2013) in this issue of Cell Host & Microbe show that the bacterial pathogens Salmonella and Brucella exploit the increased levels of glucose present in alternatively activated macrophages to sustain chronic infections in experimentally infected mice. ...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Roop RM 2nd,Caswell CC

    更新日期:2013-08-14 00:00:00

  • Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis.

    abstract::Mutations in the autophagy gene EPG5 are linked to the multisystem human disease Vici syndrome, which is characterized in part by pulmonary abnormalities, including recurrent infections. We found that Epg5-deficient mice exhibited elevated baseline innate immune cellular and cytokine-based lung inflammation and were r...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Lu Q,Yokoyama CC,Williams JW,Baldridge MT,Jin X,DesRochers B,Bricker T,Wilen CB,Bagaitkar J,Loginicheva E,Sergushichev A,Kreamalmeyer D,Keller BC,Zhao Y,Kambal A,Green DR,Martinez J,Dinauer MC,Holtzman MJ,Crouch EC

    更新日期:2016-01-13 00:00:00

  • Histone modifications and chromatin remodeling during bacterial infections.

    abstract::The link between bacteria and host chromatin remodeling is an emerging topic. The exciting recent discoveries on bacterial impact on host epigenetics, as discussed in this Review, highlight yet another strategy used by bacterial pathogens to interfere with key cellular processes. The study of how pathogens provoke hos...

    journal_title:Cell host & microbe

    pub_type: 杂志文章,评审


    authors: Hamon MA,Cossart P

    更新日期:2008-08-14 00:00:00

  • Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection.

    abstract::The transitional epithelium of the bladder normally turns over slowly but upon injury undergoes rapid regeneration fueled by basal uroepithelial stem and/or early progenitor cells (USCs). Little is known about the mechanisms underlying the injury response. We investigate the mechanism of bladder epithelial regeneratio...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Mysorekar IU,Isaacson-Schmid M,Walker JN,Mills JC,Hultgren SJ

    更新日期:2009-05-08 00:00:00

  • Epithelium, tear down this wall!

    abstract::The presence of bacteria within epithelial-lined compartments, such as the lung, elicits rapid recruitment of innate immune cells. In this issue of Cell Host & Microbe, Chun and Prince (2009) report that epithelial cells facilitate this process by reorganizing their intercellular junctions to enhance immune cell trans...

    journal_title:Cell host & microbe

    pub_type: 评论,杂志文章


    authors: Nalle SC,Turner JR

    更新日期:2009-01-22 00:00:00

  • Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner.

    abstract::The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), which naturally persists in rodents, represents a model for HIV, HBV, and HCV. Cleavage of the viral glycoprotein precursor by membrane-bound transcription factor peptidase, site 1 (Mbtps1 or site-1 protease), is crucial for the life cycle of arenavi...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Popkin DL,Teijaro JR,Sullivan BM,Urata S,Rutschmann S,de la Torre JC,Kunz S,Beutler B,Oldstone M

    更新日期:2011-03-17 00:00:00

  • Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication.

    abstract::Viral proteins have evolved to target cellular organelles and usurp their functions for virus replication. Despite the knowledge of these critical functions for several organelles, little is known about peroxisomes during infection. Peroxisomes are primarily metabolic organelles with important functions in lipid metab...

    journal_title:Cell host & microbe

    pub_type: 杂志文章


    authors: Jean Beltran PM,Cook KC,Hashimoto Y,Galitzine C,Murray LA,Vitek O,Cristea IM

    更新日期:2018-10-10 00:00:00