B-1032. CAS1 and Beijing Strains of M.tuberculosis Induce Lower Levels of TNFα and IFNγ as Compared with H37Rv in ex vivo Assays
Session: Poster Session: Innate and Adaptive Immune Responses to Infection
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: Forty four percent of M.tuberculosis isolates from Pakistan belong to the Central Asian strain (CAS1) genogroup while 3% belong to the Beijing family. Pathogenic mycobacteria are known to down-modulate protective host cytokine responses including T cell activating interferon-gamma (IFNγ) and macrophage activating tumor necrosis factor-alpha (TNFα). In this study cytokine responses stimulated by clinical strains (CAS1 and Beijing strains) in comparison to H37Rv were assessed using tissue culture and whole blood assay models. Growth curves of these strains were compared. Methods: Mycobacterium strains tested included clinical strains; 10 CAS1 and 10 Beijing strains and laboratory strain H37Rv. Mycobacterium induced TNFα responses was measured in THP-1 monocytic cells while TNFα and IFNγ responses were measured in whole blood assay (WBA) after 18 hrs of culture. Blood used was from 8 healthy endemic controls. Cytokines (TNFα and IFNγ) were measured using ELISA. Mycobacterium growth curve was measured for up to 30 days for each strain in the BACTEC MGIT 960 system. Results: The predominant genogroups in our population induced significantly lower TNFα secretion in THP-1 cells and whole blood cells (CAS1; P<0.01, Beijing; P<0.01) in comparison with H37Rv. Similarly IFNγ induction by the clinical strains (CAS1; P<0.01, Beijing; P<0.01) in whole blood assay was significantly lower when compared with reference strain (H37Rv). Furthermore growth rates of CAS1 and Beijing strains were also noted to be reduced in relation to H37Rv (P<0.01). Conclusion: Our results suggest that the ability of prevalent clinical strains of CAS1 and Beijing genogroups to down regulate critical host immune mediators TNFα and IFNγ may confer a selective advantage to them. We further hypothesis that the lower growth rate of these strains may be a contributory factor for the reduced cytokine responses and enhance their survival in this population.
Akbar Kanji, MSc1, Mahnaz Tanveer, MSc1, Rabia Hussain, PhD, FRC Path2, Rumina Hasan, MBBS, PhD, FRCPath3, Zahra Hasan, PhD4 and  R. Hasan, None., (1)Aga Khan University, (2)THE AGA KHAN UNIVERSITY, Karachi, Pakistan, (3)Aga Khan University, Karachi, Pakistan, (4)THE AGA KHAN UNIVERSITY, Karachi-74800, Pakistan