Innate immune system provides the first line of defense against pathogenic organisms. It has a varied and large collection of molecules known as pattern recognition receptors (PRRs) which can tackle the pathogens promptly and effectively. Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are members of the PRR family that recognize pathogen associated molecular patterns (PAMPs) and play pivotal roles to mediate defense against infections from bacteria, fungi, virus and various other pathogens. In this review, we discuss the critical roles of TLRs and NLRs in the regulation of host immune-effector functions such as cytokine production, phagosome-lysosome fusion, inflammasome activation, autophagy, antigen presentation, and B and T cell immune responses that are known to be essential for mounting a protective immune response against the pathogens. This review may be helpful to design TLRs/NLRs based immunotherapeutics to control various infections and pathophysiological disorders.

Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, is one of the most successful pathogens in human history. An extremely resilient cell wall and highly evolved and coordinated strategies for immune evasion have made it a very formidable pathogen. The secretory proteins of M. tuberculosis play a crucial role in its virulence and immune evasion. The secretory proteins are secreted through tightly regulated secretion systems and modulate the host immune responses through a plethora of strategies, including epigenetic reprogramming of infected cells, targeting antigen presentation, inhibition of phagosomal maturation, modulation of cytokine production, apoptosis and redox regulation, etc. Upon infection, the secretory proteins become localized into various cellular organelles, such as nucleus, cytoplasm, phagosomes and Golgi, bodies and hijack the host machineries through their wide gamut of functions, including kinase, phosphatase, methyl transferase activities and interaction with several host partners. In this review, we discuss the secretion systems, the functions of various secretory proteins of M. tuberculosis and their roles in modulating immune responses of the host. We also discuss the feasibility of their use as possible therapeutic targets. This information is likely to improve our understanding of the host–pathogen interaction and help in the design of effective anti‐tuberculosis therapeutics.

Tuberculosis (TB) is one of the oldest human diseases and is one of the major causes of mortality and morbidity across the Globe. Mycobacterium tuberculosis (Mtb), the causal agent of TB is one of the most successful pathogens known to mankind. Malnutrition, smoking, co-infection with other pathogens like human immunodeficiency virus (HIV), or conditions like diabetes further aggravate the tuberculosis pathogenesis. The association between type 2 diabetes mellitus (DM) and tuberculosis is well known and the immune-metabolic changes during diabetes are known to cause increased susceptibility to tuberculosis. Many epidemiological studies suggest the occurrence of hyperglycemia during active TB leading to impaired glucose tolerance and insulin resistance. However, the mechanisms underlying these effects is not well understood. In this review, we have described possible causal factors like inflammation, host metabolic changes triggered by tuberculosis that could contribute to the development of insulin resistance and type 2 diabetes. We have also discussed therapeutic management of type 2 diabetes during TB, which may help in designing future strategies to cope with TB-DM cases.