Major histocompatibility complex restriction in tuberculosis susceptibility

Pitchappan, R. M.; Agrewala, Javed N.; Dheenadhayalan, Veerabadran; Iványi, Juraj

doi:10.1007/bf02703617

Cited by 3 publications

(3 citation statements)

References 14 publications

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“…MHC, TLR-2, Vitamin D receptor, IFN-γ, IL-12R etc. [4], [5], [6]. It was initially believed that MTB complex constituted a genetically highly conserved group of bacteria, hence most of the earlier immunological studies have used a limited number of laboratory strains, such as H37Ra, H37Rv, Erdman and CDC1551 [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Drug Resistant Clinical Isolates of Mycobacterium tuberculosis from Different Genotypes Exhibit Differential Host Responses in THP-1 Cells

et al. 2013

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Mycobacterium tuberculosis (MTB) persistently infects and survives within the host macrophages. Substantial genotypic variation exists among MTB strains which correlate with their interactions with the host. The present study was designed to establish a correlation, if any, between infection and induction of innate immune response by genetically diverse drug resistant MTB isolates from India. For this purpose, three clinical isolates from ancient and modern lineages, along with H37Ra and H37Rv were evaluated for intracellular growth, phagocytic index, induction of proinflammatory cytokines and apoptosis following infection in THP-1 cell line. A wide variation in the induction of cytokines was revealed subsequent to infection with different strains. EAI-5 strain from ancient lineage 1, induced higher proinflammatory responses, higher apoptosis and moderate intracellular growth compared to other strains, in contrast, for Beijing strain of modern lineage 2, all three parameters were lowest among the clinical isolates. Further, the responses induced by LAM-6 from modern lineage 4 were at a moderate level, similar to the laboratory strain H37Rv which also belongs to lineage 4. Thus, these profiles were specific to their respective lineages and/or genotypes and independent of their drug resistance status. Further, a positive correlation, among TNF-α, IL-1β, IL-6 and IL-12 induced in infected THP-1 cells was demonstrated. In addition, induction of all pro-inflammatory cytokines correlated well with the host cell apoptosis. A positive correlation was observed between phagocytic index in the category of ‘>10 bacilli/cell’ and induction of apoptosis, only for virulent strains, indicating that initial accumulation of MTB strains inside the host cell may be an important determining factor for different innate responses.

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Section: Introductionmentioning

confidence: 99%

Drug Resistant Clinical Isolates of Mycobacterium tuberculosis from Different Genotypes Exhibit Differential Host Responses in THP-1 Cells

et al. 2013

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“…Several studies have also investigated the possible role of HLA alleles in the incidence and progression of TB. For instance, some studies from India and other countries have reported different HLA alleles that are associated with incidence and progression of TB [ 6 , 22 – 24 ], particularly the association of DRB*1501 with advanced disease and failure to respond to drug therapy. Other studies from India and elsewhere have noted a lower incidence of TB disease among adult females than in adult males, compared to children and adolescents.…”

Section: Discussionmentioning

confidence: 99%

HLA-B∗57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Jagannathan¹,

Chaturvedi²,

Bhuthaiah³

et al. 2011

Clinical and Developmental Immunology

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Background. Substantial evidence exists for HLA and other host genetic factors being determinants of susceptibility or resistance to infectious diseases. However, very little information is available on the role of host genetic factors in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate HLA associations in a cohort of HIV seropositive individuals with and without TB in Bangalore, South India. Methods. A cohort of 238 HIV seropositive subjects were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors was used as control. Results. The ratio of males and females in HIV cohort was comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in females (12.6%,) than males (25.6%). Further, HLA-B*57 frequency in HIV cohort was significantly higher among females without TB (21.6%, 19/88) than males (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in this cohort. Conclusion. This study suggests that HIV positive women with HLA-B*57 have less occurrence of TB as compared to males.

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“…The search for such T-cell epitopes on the PstS1 antigen so far did not yield supportive data. Epitope specificity was determined only for Th1 cell clones which were mostly HLA-DR promiscuous ( 82 ) with all immunodominant epitopes of PstS1 binding to several HLA-DR molecules ( 22 ). However, these assays may not be suitable to reveal a DR2-restricted presentation of the same epitope to Th2 T cells.…”

Section: Association Of Hla-dr and Antibody Epitope Specificity With mentioning

confidence: 99%

Function and Potentials of M. tuberculosis Epitopes

Iványi

2014

Front. Immunol.

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Study of the function of epitopes of Mycobacterium tuberculosis antigens contributed significantly toward better understanding of the immunopathogenesis and to efforts for improving infection and disease control. Characterization of genetically permissively presented immunodominant epitopes has implications for the evolution of the host–parasite relationship, development of immunodiagnostic tests, and subunit prophylactic vaccines. Knowledge of the determinants of cross-sensitization, relevant to other pathogenic or environmental mycobacteria and to host constituents has advanced. Epitope-defined IFNγ assay kits became established for the specific detection of infection with tubercle bacilli both in humans and cattle. The CD4 T-cell epitope repertoire was found to be more narrow in patients with active disease than in latently infected subjects. However, differential diagnosis of active TB could not be made reliably merely on the basis of epitope recognition. The mechanisms by which HLA polymorphism can influence the development of multibacillary tuberculosis (TB) need further analysis of epitopes, recognized by Th2 helper cells for B-cell responses. Future vaccine development would benefit from better definition of protective epitopes and from improved construction and formulation of subunits with enhanced immunogenicity. Epitope-defined serology, due to its operational advantages is suitable for active case finding in selected high disease incidence populations, aiming for an early detection of infectious cases and hence for reducing the transmission of infection. The existing knowledge of HLA class I binding epitopes could be the basis for the construction of T-cell receptor-like ligands for immunotherapeutic application. Continued analysis of the functions of mycobacterial epitopes, recognized by T cells and antibodies, remains a fertile avenue in TB research.

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Major histocompatibility complex restriction in tuberculosis susceptibility

Cited by 3 publications

References 14 publications

Drug Resistant Clinical Isolates of Mycobacterium tuberculosis from Different Genotypes Exhibit Differential Host Responses in THP-1 Cells

Drug Resistant Clinical Isolates of Mycobacterium tuberculosis from Different Genotypes Exhibit Differential Host Responses in THP-1 Cells

HLA-B∗57 and Gender Influence the Occurrence of Tuberculosis in HIV Infected People of South India

Function and Potentials of M. tuberculosis Epitopes

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