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    Dissecting immunity in the bladder

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    Séminaire de l'Institut Cochin

    Lundi 20 janvier 2020 - 12h00 - Salle de conférence Rosalind Franklin, 2ème étage

     


    Molly Ingersoll

    Institut Pasteur, Inserm U1223, Paris

     

     invitée par Florence Niedergang

    Institut Cochin, 22 rue Méchain, 75014 Paris

     

    Résumé

    The most prevalent diseases of the bladder are urinary tract infection (UTI), affecting ~50% of adult women and non-muscle invasive bladder cancer (NMIBC), the 4th most common malignancy in men. While UTI and NMIBC are seemingly disparate illnesses, one commonality is the interaction of bacteria with the bladder mucosa, as the first step in infection or repeatedly as immunotherapy for cancer. Notably, however, UTI and BCG immunotherapy induce different immunologic outcomes. We model both diseases to delineate the immune response in the bladder, particularly with respect to macrophage function and sex differences. As an example, otherwise healthy, premenopausal women have a significantly higher incidence of UTI than men, yet, male UTI is more persistent with greater associated morbidity. Additionally, both sexes are at risk of recurrence, suggesting that adaptive immunity to UTI is insufficient. We identified mechanisms that govern a sex biased immune response to UTI. Currently, we are dissecting the initial events leading to a specific effector cell response and how this response can be immunomodulated for improved therapeutics that obviate the need for antibiotics to treat multidrug resistant uropathogens and may also be employed to improve treatment for bladder cancer.

     

    Bio

    Dr. Molly Ingersoll received her PhD studying host-pathogen interactions from NYU School of Medicine working with Arturo Zychlinsky at NYU and at the Max Planck Institute for Infection Biology in Berlin, Germany. A brief postdoctoral fellowship at Washington University School of Medicine, in St Louis, MO with Scott Hultgren, studying innate immunity to urinary tract infection was followed by a postdoctoral appointment at Mount Sinai Medical Center in NYC, investigating monocyte and dendritic cell biology. Dr. Ingersoll currently heads a team interested in immunity in the bladder in the context of infection and cancer at the Institut Pasteur in Paris.

     

    Quelques publications

    1. Sex differences in IL-17 contribute to chronicity in male versus female urinary tract infection. Zychlinsky Scharff A, Rousseau M, Lacerda Mariano L, Canton T, Consiglio CR, Albert ML, Fontes M, Duffy D, Ingersoll MA. JCI Insight. 2019 May 30;5. pii: 122998. doi: 10.1172/jci.insight.122998. PMID: 31145099

    2. Mechanisms of BCG immunotherapy and its outlook for bladder cancer. Pettenati C, Ingersoll MA. Nat Rev Urol. 2018 Oct;15(10):615-625. doi: 10.1038/s41585-018-0055-4. PMID: 29991725

    3. Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection. Tien BYQ, Goh HMS, Chong KKL, Bhaduri-Tagore S, Holec S, Dress R, Ginhoux F, Ingersoll MA, Williams RBH, Kline KA. Infect Immun. 2017 Nov 17;85(12). pii: e00378-17. doi: 10.1128/IAI.00378-17. Print 2017 Dec. PMID: 28893918

    4. Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment. Rousseau M, Goh HMS, Holec S, Albert ML, Williams RB, Ingersoll MA, Kline KA. JCI Insight. 2016 Sep 22;1(15):e88178. doi: 10.1172/jci.insight.88178. PMID: 27699248

    5. Macrophages Subvert Adaptive Immunity to Urinary Tract Infection. Mora-Bau G, Platt AM, van Rooijen N, Randolph GJ, Albert ML, Ingersoll MA. PLoS Pathog. 2015 Jul 16;11(7):e1005044. doi: 10.1371/journal.ppat.1005044. eCollection 2015 Jul. PMID: 26182347 

     

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