Mycobacterium tuberculosis LprE enhances bacterial persistence by inhibiting cathelicidin and autophagy in macrophages

Padhi, Avinash; Bhagyaraj, Ella; M, Zahoor Khan; Biswas, Mainak; Sengupta, Srabasti; Ganguli, Geetanjali; Jagadev, M; Behera, Ananyaashree; Pattanaik, Kali Prasad; Das, Indraneil; Gupta, Pawan; Vk, Nandicoori; Sonawane, Avinash

doi:10.1101/230698

Cited by 1 publication

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“…The non-pathogenic species induce strong autophagic response in macrophages whereas pathogenic ones are known to suppress autophagy which form a part of their survival strategies within the host cells. However, this suppression/ inhibition of autophagy is caused by certain mycobacterial components including lipoproteins (LpqH, LprE) and glycolipids (phosphatidyl-myo-inositol mannosides, lipomannans, lipoarabinomannan) which have the ability to limit host autophagy responses to the pathogens [15,[21][22][23][24]. In recent past, we have reported MIP to be a potent inducer of autophagy.…”

Section: Discussionmentioning

confidence: 99%

Lipoarabinomannan from Mycobacterium indicus pranii shows immunostimulatory activity and induces autophagy in macrophages

et al. 2019

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Mycobacterium indicus pranii (MIP) known for its immunotherapeutic potential against leprosy and tuberculosis is undergoing various clinical trials and also simultaneously being studied in animal models to get insight into the mechanistic details contributing to its protective efficacy as a vaccine candidate. Studies have shown potential immunomodulatory properties of MIP, the most significant being the ability to induce strong Th1 type of response, enhanced expression of pro-inflammatory cytokines, activation of APCs and lymphocytes, elicitation of M.tb specific poly-functional T cells. All of these form crucial components of host-immune response during M.tb infection. Also, MIP was found to be potent inducer of autophagy in macrophages which resulted in enhanced clearance of M.tb from MIP and M. tb co-infected cells. Hence, we further examined the component/s of MIP responsible for autophagy induction. Interestingly, we found that MIP lipids and DNA were able to induce autophagy but not the protein fraction. LAM being one of the crucial components of mycobacterial cell-wall lipids and possessing the ability of immunomodulation; we isolated LAM from MIP and did a comparative study with M.tb-LAM. Stimulation with MIP-LAM resulted in significantly high secretion of pro-inflammatory cytokines and displayed high autophagy inducing potential in macrophages as compared to M.tb-LAM. Treatment with MIP-LAM enhanced the co-localization of M.tb within the phago-lysosomes and increased the clearance of M.tb from the infected macrophages. This study describes LAM to be a crucial component of MIP which has significant contribution to its immunotherapeutic efficacy against TB.

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