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Mycobacterium tuberculosis strategy to protect itself from host defence.

Over the years different microbes are applying different strategies to protect itself from host defence. Just like any other complex organisms microorganisms too adapt itself depending on various host defence mechanism and are incorporating different gene sequences which code for different proteins that helps microbes to fool our defence immune system. Out of various strategies molecular mimicry is one of the most prevalent strategies used by different microorganisms. In this report, we are going to briefly understand how Mycobacterium tuberculosis uses molecular mimicry to protect itself from innate immune response.

What is molecular mimicry?

As indicated by the name molecular mimicry is nothing but mimicking host proteins by incorporating gene sequence that code for a protein similar to the host proteins. This strategy helps in modulating  immune response mainly observed in innate immune response.

What are Toll like receptors (TLR)?

TLRs are pattern recognition receptors which are mostly present in dendritic cells, macrophages recognise pathogen associated molecular patterns like lipid, protein, nucleic acid present in the structure of the microbe, led the activation of both innate and adaptive immune response.

Fig structure of TLR1-TLR2 heterodimer which are mainly involved in innate immune response

What is adaptor protein like MYD88?

MYD88 is an adaptor protein which contains a toll interleukin-1 receptor domain which when activated helps in protein-protein interaction for signal transduction like activation of NF-kB.

Flowchart of TLR signalling pathway in innate immune response

MyD88 adaptor protein similarity with M. tuberculosis proteins Rv3529c

When the researchers performed local alignment of 6 isoforms of human MyD88 adaptor protein with M. tuberculosis proteins Rv3529c in National Center for Biotechnology Information and Protein Data Bank database using NCBI PSI BLAST they found that Rv3529c, protein have high similarity in the secondary structure within the death domain of MyD88 protein.

What are the mechanisms inhibited by the Rv3529c protein?

  1. Rv3529c protein interferes with the  associations between MyD88 with IRAK1

When macrophages were stimulated with Rv3529c protein , it inhibits the association of MyD88 and IRAK1 because of its similarity with MyD88. The direct association of Rv3529c with IRAK1 effects on macrophage defense responses to M. tuberculosis.

  • Rv3529c inhibits TLR2 induced oxidative burst in Macrophages

It is well known that macrophage early defence mechanism is to generate reactive oxygen species against the pathogen. Researchers observed that when macrophages are stimulated with Rv3529c the toll like receptor induced ROS level was seen to get inhibited. When calcium release from intracellular stores was inhibited along with induction of Rv3529c  protein The  ROS level was inhibited whereas inhibition of calcium influx from the external medium didn’t have any impact on ROS, thus it indicated that the route of calcium entry plays a crucial role in ROS inhibition.

  • Rv3529c inhibits TLR2-mediated activation of NF-kB

NF-kB protein complex, which is mainly involved in the transcription of genes involved in cytokine production required for generating a strong immune response, is inhibited when Rv3529c is induced to a macrophage. It was observed by the researchers that Rv3529c significantly inhibited TLR2-mediated phosphorylation of ERK- MAPK which is required for the activation of NF-kB.

  • Rv3529c inhibits production of proinflammatory cytokines

Proinflammatory cytokines are proteins which promote inflammatory response when there is an entry of pathogen. Example IFN-g, IL-6, and IL17A, Just like proinflammatory cytokines there are also cytokine which supress inflammation in order to regulate the process of inflammation, example IL-10 and TGF-b. It was observed by the researchers that the stimulation with Rv3529c, significantly decreased the expression of IFN-g, IL-6, and IL-17A as well as significantly increasing the levels of IL-10 and TGF-b. Thus these results suggested  that the Rv3529c is enhancing suppressor responses from macrophages which helps pathogen like M. tuberculosis to protect itself from host defence.


As discussed above these are some strategies which promotes the survival of M. tuberculosis in host by inhibiting protective responses and creating a niche for the pathogen for long-term survival. It was observed that Rv3529c protein not only helped M. tuberculosis but also helps in the  survival of M. bovis BCG in infected macrophages. Rv3529c significantly increased colony forming unit of these pathogens, which indicates a direct role of Rv3529c in regulating mycobacterial survival within macrophages. Though the mechanisms involved during the immune suppression by Rv3529c, is not known yet researchers are trying to understand the mechanism which involves various signalling pathways and also primary genes which mediate protective responses.


Bandyopadhyay, U., Chadha, A., Gupta, P., Tiwari, B., Bhattacharyya, K., Popli, S., Raman, R., Brahamachari, V., Singh, Y., Malhotra, P. and Natarajan, K., 2017. Suppression of Toll‐like receptor 2–mediated proinflammatory responses by Mycobacterium tuberculosis protein Rv3529c. Journal of leukocyte biology, 102(5), pp.1249-1259.

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  • I know it's bad to human beings, but these mechanisms of M. tuberculosis are amazing. I always think that bacteria and viruses are so tiny, but they have very interesting modus operandi... Microbiology is really amazing!!

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