Group Leader: Dr. Nirmal Robinson
Tripti Mishra (-32230)
Inflammation, cell death and phagosomal processing in the innate immune response against intracellular bacterial pathogens
Innate immunity provides the first line of immune defence against pathogens and facilitates the development of acquired immune response which controls pathogens comprehensively. Although many of the invading pathogens are controlled by the innate immune system, some pathogenic species of Mycobacterium, Salmonella and Listeria have evolved successful strategies to evade the host’s innate immune response.
The persevering interest of the group is to understand the underlying molecular mechanisms that regulate the innate immune response against intracellular bacterial pathogens and to unravel the immune evasive mechanisms employed by these pathogens.
Salmonella enterica serovar Typhimurium (ST) is a gram negative, facultative intracellular pathogen that intervenes with key innate immune responses:
(i) It efficiently employs type III secretion system encoded in the Salmonella pathogenecity island (SPI)-2 to evade phagosomal processing and replicate in the innate immune cells.
(ii) Pathogen associated molecular patterns (PAMPs) of ST engage with different pattern recognition receptors (PRRs) resulting in elevated inflammation. Subsequently, the susceptible host succumb to death predominantly due to overt inflammation.
(iii) ST also evades innate immune defence by inducing an atypical cell death in macrophages which is a result of PRR engagement and inflammation.
Our recent studies revealed that ST exploits IFN-I signalling to induce an atypical inflammatory cell death in macrophages, thus evading the innate immune defence. Our preliminary findings also suggest that molecular regulators that govern the cell death pathways also regulate the inflammatory pathways.
Our current objective is to study the cross-talk between different cell death and inflammatory pathways and their role in the innate immune response against ST and innate-immunesenescence.
Nirmal Robinson, Scott McComb, Rebecca Mulligan, Renu Dudani, Lakshmi Krishnan and Subash Sad. Type-I interferon induces necroptosis in macrophages during Salmonella Typhimurium infection. Nat Immunol. 2012 Aug 26. doi: 10.1038/ni.2397. [Epub ahead of print]
Jan Rybniker, Angela Nowag, Edeltraud van Gumpel, Nicole Nissen, Nirmal Robinson, Georg Plum and Pia Hartmann. Insights into the function of the WhiB-like protein of mycobacteriophage TM4 – a transcriptional inhibitor of WhiB2. Mol Microbiol. 2010 August;77(3):642-657.
Anindita Chattopadhyay, Nirmal Robinson, Jagdeep K. Sandhu, B Brett Finlay, Subash Sad and Lakshmi Krishnan. Salmonella Typhimurium induced placental inflammation and not bacterial burden correlates with pathology and fatal maternal disease. Infect Immun. 2010 May;78(5): 2292-301.
Homam Albaghdadi, Nirmal Robinson, Renu Dudani, Lakshmi Krishnan and Subash Sad. Selectively reduced intracellular proliferation of Salmonella Typhimurium within antigen-presenting cells limits antigen-presentation and development of a rapid CD8 T cell response. J Immunol. 2009 Sep 15;183(6):3778-87.
Nirmal Robinson, Thomas Kolter, Jan Rybniker, Martina Wolke, Pia Hartmann, Georg Plum. A Mycobacterial glycolipid inhibits phagosome maturation and subverts proinflammatory cytokines. Traffic. 2008 Nov; 9(11): 1936-47.
Jan Rybniker, Georg Plum, Nirmal Robinson, Pamela L. Small and Pia Hartmann. Identification of three cytotoxic early proteins of mycobacteriophage L5 leading to growth inhibition in Mycobacterium smegmatis. Microbiology. 2008 Aug; 154 (Pt 8): 2304-14.
Nirmal Robinson, Martina Wolke, Karen Ernestus and Georg Plum. A Mycobacterial Gene Involved in Synthesis of an Outer Cell Envelope Lipid is a Key Factor in Prevention of Phagosome Maturation. Infect Immun. 2007 Feb; 75(2):581-91.
Tom Li Stephen, Mario Fabri, Laura Groneck, Till A. Röhn, Helena Hafke, Nirmal Robinson, Jens Rietdorf, David Schrama, Jürgen C. Becker, Georg Plum, Martin Krönke, Harald Kropshofer, and Wiltrud M. Kalka-Moll. Transport of Streptococcus pneumoniae Capsular Polysaccharide in MHC Class II Tubules. PLoS Pathog. 2007 Mar 16;3(3):e32.