The Man Group investigates the role of innate immunity in infectious diseases and cancer. Pattern-recognition receptors are germ-line encoded innate immune sensors which detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). These receptors activate signalling pathways and mediate the production of inflammatory cytokines, type I interferons and other anti-microbial molecules. We use cutting-edge technology to study the mechanisms by which host sensors recognise bacteria, viruses and parasites, and how these sensors shape the overall immune response to infection. We also study the molecular basis by which uncontrolled inflammation can lead to the development of cancer, autoimmunity and inflammatory diseases.
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Man, SM,* Karki, R,* Sasai, M, Place, DE, Kesavardhana, S, Temirov, J, Frase, S, Zhu, Q, Malireddi, RKS, Kuriakose, T, Peters, JL, Neale, G, Brown, SA, Yamamoto, M and Kanneganti, TD (2016) IRGB10 liberates bacterial ligands for sensing by the AIM2 and caspase-11–NLRP3 inflammasomes. Cell 167:382–396 *Co-first author
Man, SM,* Zhu, Q,* Zhu, L,* Liu, Z,* Karki, R, Malik, A, Sharma, D, Li, L, Malireddi, RKS, Gurung, P, Neale, G, Olsen, SR, Carter, RA, McGoldrick, DJ, Wu, G, Finkelstein, D, Vogel, P, Gilbertson, RJ and Kanneganti, TD (2015) Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell 162:45-58 *Co-first author
Karki, R,* Man, SM,* Malireddi, RKS, Kesavardhana, S, Zhu, Q, Burton, AR, Sharma, BR, Pelletier, S, Vogel, P, Rosenstiel, P and Kanneganti, TD (2016) NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer. Nature 540:583–587 *Co-first author
Man, SM, Karki, R, Malireddi, RKS, Neale, G, Vogel, P, Yamamoto, M, Lamkanfi, M and Kanneganti, TD (2015) The transcription factor IRF1 and guanylate-binding proteins target AIM2 inflammasome activation by Francisella infection. Nature Immunology 16:467–475
Man, SM, Hopkins, LJ, Nugent, E, Cox, S, Gluck, IM, Tourlomousis, P, Wright, JA, Cicuta, P, Monie, TP and Bryant, CE (2014) Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex. Proc Natl Acad Sci USA 111: 7403-7408
Man, SM,* Ekpenyong, AE,* Tourlomousis, P, Achouri, S, Cammarota, E, Hughes, K, Rizzo A, Ng, G, Wright, JA, Cicuta, P, Guck, J and Bryant, CE (2014) Actin polymerization as a key innate immune effector mechanism to control Salmonella infection. Proc Natl Acad Sci USA 111:17588–17593 *Co-first author
Man, SM and Kanneganti, TD (2016) Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nature Reviews Immunology 16:7-21
Man, SM (2011) The clinical importance of emerging Campylobacter species. Nature Reviews Gastroenterology & Hepatology 8:669-685
Man, SM, Kaakoush, NO, Mitchell, HM (2011) The role of bacteria and pattern-recognition receptors in Crohn’s disease. Nature Reviews Gastroenterology & Hepatology 8:152-168
Qi, X,* Man, SM,* Malireddi, RKS, Karki, R, Lupfer, C, Gurung, P, Neale, G, Guy, CS, Lamkanfi, M and Kanneganti, TD (2016) Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. Journal of Experimental Medicine 213:2081-2097 *Co-first author
Kuriakose, T, Man, SM, Malireddi, RKS, Karki, R, Kesavardhana, S, Place, DE, Neale, G, Vogel, P, Kanneganti, TD (2016) ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Science Immunology 1:aag2045
Karki, R, Man SM, Malireddi, RKS, Gurung, P, Vogel, P, Lamkanfi, M and Kanneganti, TD (2015) Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection. Cell Host & Microbe 17:357-368
Kaakoush, NO, Castaño Rodriguez, N, Mitchell, HM and Man, SM ‡ (2015) Global epidemiology of Campylobacter infection. Clinical Microbiology Reviews 28:687-720 ‡ Corresponding author
Kaakoush, NO, Castaño Rodriguez, N, Man, SM and Mitchell, HM (2015) Is Campylobacter to esophageal adenocarcinoma as Helicobacter is to gastric adenocarcinoma? Trends in Microbiology 23:455-462