Eis (enhanced intracellular survival) protein of Mycobacterium tuberculosis disturbs the cross regulation of T-cells.
The pathogenesis of tuberculosis is complex and its manifestations diverse, reflecting a lifetime of dynamic interactions between mycobacterial virulence factors and the human immune system. The pathogenic mycobacteria have developed strategies to circumvent the major killing mechanisms employed by macrophages and take advantage of the enclosed environment within its host cell to avoid humoral and cell-mediated immune responses. Secretory proteins play a major role in host-pathogen interactions. The eis (Rv2416c) gene has been identified as a secretory protein, and it has been shown that it enhances intracellular survival of Mycobacterium semgmatis in the macrophage cell line. The main aim of this study was to gain insight into the biological role of Eis in the host. Stimulation of T-cells with Eis recombinant protein of Mycobacterium tuberculosis inhibits Con A-mediated T-cell proliferation in vitro. Treatment of T-cells with Eis inhibits ERK1/2, JAK pathway, and subsequent production of tumor necrosis factor-alpha and interleukin-4. On the contrary, there is increased production of interferon-gamma and interleukin-10, which indicates that immunity in response to Eis treatment is skewed away from a protective T(H)1 response and Eis disturbs the cross regulation of T-cells.
Lella
Ravi K
RK
Drug Target Discovery and Development Division, Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001, U.P. India.
Sharma
Charu
C
D000123:Acetyltransferases; D000942:Antigens, Bacterial / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity*; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology*; D014774:Virulence
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; D000123:Acetyltransferases; C430563:Eis protein, Mycobacterium tuberculosis; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3