Host–Pathogen Interactions in Tuberculosis (original) (raw)
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Crosstalk between Mycobacterium tuberculosis and the host cell
The successful establishment and maintenance of a bacterial infection depend on the pathogen’s ability to subvert the host cell’s defense response and successfully survive, proliferate, or persist within the infected cell. To circumvent host defense systems, bacterial pathogens produce a variety of virulence factors that potentiate bacterial adherence and invasion and usurp host cell signaling cascades that regulate intracellular microbial survival and trafficking. Mycobacterium tuberculosis, probably one of the most successful pathogens on earth, has coexisted with humanity for centuries, and this intimate and persistent connection between these two organisms suggests that the pathogen has evolved extensive mechanisms to evade the human immune system at multiple levels. While some of these mechanisms are mediated by factors released by M. tuberculosis, others rely on host components that are hijacked to prevent the generation of an effective immune response thus benefiting the survival of M. tuberculosis within the host cell. Here, we describe several of these mechanisms, with an emphasis on the cyclic nucleotide signaling and subversion of host responses that occur at the intracellular level when tubercle bacilli encounter macrophages, a cell that becomes a safe-house for M. tuberculosis although it is specialized to kill most microbes.
Interconnection of Mycobacterium tuberculosis with host immune system
Journal of Respiratory Diseases and Medicine, 2020
Precise estimation of development of active tuberculosis (TB) infection from a latent Mycobacterium tuberculosis H 37 Rv (MTB) infection within host body signifies an indefinable and serious objective. Most of the infected individuals with excellent immune system are also at risk due to diverse local environmental and systemic factors. Therefore, it becomes mandatory to have a balance between pro and anti-immune regulators to work efficiently in optimized manner. This study thus signifies some essential factors involved in maintaining this balance and rescue host cellular environment from MTB infection. Inside host, MTB develops effective survival strategies, such as hampering of lysosome-phagosome fusion, hampering of phagosome acidification by a secretary protein phosphatase PtpA that binds to H subunit of V-ATPase to block V-ATPase transportation towards phagosome membrane, recruitment of TACO protein on phagosomal membrane to escape their transportation to lysosome. Bacterial infected cell undergoing apoptosis release ATP, UTP, LPC, S1P and several chemokines that intervene signaling of "find me" signal. Eventually, a balance between all these immunological factors must be set for optimized functioning of immune system against MTB. In this review we have elaborated various balancing mechanisms among pro and anti-inflammatory immune components that raise this disease from latent to active form. Through a brief and complete evaluation of different types of immune components that take part in host defense, we aimed to highlight the review with recent documented literatures to have a better and precise understanding of this disease. In conclusion, this review abridges various defensive strategies that moderate the distinct capability to fight MTB infection.
Unique Characteristic Features of Mycobacterium Tuberculosis in Relation to Immune System
American Journal of Immunology, 2011
Problem statement: Tuberculosis is a leading global mortality factor which has not been effectively controlled, with 1.7 million deaths per year and 8.9 million new cases. Aerobic microbe Mycobacterium Tuberculosis H37Rv (MTB) is the causative agent of tuberculosis. Approach: It is unique among prokaryotes due to its exceptional features contributing to its survival within the hostile environment of macrophages. Results: It modifies both its intracellular and local tissue environment and proliferates within macrophages resulting in caseous granulomas, the characteristic lesions of TB. MTB derived cAMP intoxicates host cells and thus enable MTB for long term persistence within macrophages by modifying its intracellular environment. Apart from these, there are several unique structural components of MTB which interfere in the pathways of immune system and thus eluding it from destruction. Conclusion: The dormant state of MTB is the major factor which provides this pathogen ability to survive host inflammatory mediators and antibiotic treatment. It is indispensable to delineate the unusual features of MTB that enable its escape from the host immune system, in order to design an efficacious drug against the unpardonable form of tuberculosis.
An approach for studying the mediators of pathogenesis inMycobacterium tuberculosis
Journal of Biosciences, 1996
Mycobacterium tuberculosis is an example of an intracellular pathogen that mediates the disease state through complex interactions with the host's immune system. Not only does this organism replicate in the hostile environment prevailing within the infected macrophage, but it has also developed intricate mechanisms to inhibit several defence mechanisms of the host's immune system. It is postulated here that the mediators of these interactions with the host are products of differentially expressed genes in the pathogen. Β and Τ cell responses of the host are hence to be used as tools to identify such gene products from an expression library of the Mycobacterium tuberculosis genome. The various pathways of generating a productive immune response that may be targeted by the pathogen are discussed.
Virulence factors of the Mycobacterium tuberculosis complex
Virulence, 2013
The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world.
Bioinformation, 2015
Mycobacterium tuberculosis is known to be associated with several autoimmune diseases such as systemic lupus erythematous, rheumatoid arthritis and multiple sclerosis. This is attributed to sequence similarity between virulent factors and human proteins. Therefore, it is of interest to identify such regions in the virulent factors to assess potential autoimmune related information. M. tb specific virulent factors were downloaded from the VFDB database and its human homologs were identified using the sequence comparison search tool BLASTP. Both virulent proteins and their corresponding human homologs were further scanned for epitopes (B cell and HLA class I and II allele specific) using prediction programs (BCPRED and NETMHC). Data shows the presence of matching 22 B-cell, 79 HLA class II and 16 HLA class I specific predicted epitopes in these virulent factors having human homologs. A known peptide (HAFYLQYKNVKVDFA) associated with autoimmune atopic dermatitis is shown in the superoxide dismutase homolog structures of the bacterium (PDB ID: 1IDS) and human (PDB ID: 2QKC). This data provides insight into the understanding of infection-associated auto-immunity Background: Pathogenic intracellular organisms have strategies of evading or suppressing the host's immune response. Strategies against acquired immunity include antigenic variation, immune suppression and molecular mimicry. Molecular mimicry is well documented in viruses such as HIV, monkey pox and cow pox and its primary function is camouflage [1, 2]. Molecular mimicry can be defined as sequence or structural similarity between host and pathogen peptides resulting in immune evasion or cross reactivity leading to autoimmune response. Pathogens may also mimic host molecules to manipulate factors in signal transduction pathways via their receptors [3-6]. Previous studies have shown that cross reactive antibodies are produced in response to bacterial infections causing tissue damage [7-9]. Tuberculosis (TB) has been associated with several autoimmune diseases such as systemic lupus erythematous, rheumatoid arthritis and multiple sclerosis [10-18]. M. tb induced T cell reactivity with foreign and self-antigens lead to autoimmune responses [11, 14, 15, 17]. Thus, detecting epitopes involved in cross reactivity could help in comprehending TB immuno-pathogenesis. The present study identified epitopes with sequence and structural similarities between M. tuberculosis virulent factors and host homologs for B-cells and T-cells (class I and II HLA alleles) specificity [19, 20] Methodology: Virulent Factors Database (VFDB) M.tb specific virulent factors (number) were downloaded in FASTA format from VFDB (a database of virulent factors) [21]. Basic Local Alignment Search Tool (BLAST)-2.2.28 The Basic Local Alignment Search Tool (BLAST) is used to find regions of local similarity between M.tb virulent factor and human proteome [22].