02837nas a2200373 4500000000100000008004100001260001300042653001200055653001900067653002100086653002100107653002000128653001600148653000900164653003100173653001900204653001700223653001700240100001300257700001300270700001600283700001200299700001800311700001400329700001500343700001500358700001300373700001600386245018300402300000900585490000700594520184800601022001402449 2013 d c2013 Jan10aAnimals10aBacterial Load10aChemokine CXCL1010aChemokine CXCL1110aGene Expression10aGuinea Pigs10aLung10aMycobacterium tuberculosis10aRNA, Messenger10aTime Factors10aTuberculosis1 aRawat KD1 aChahar M1 aReddy P V J1 aGupta P1 aShrivastava N1 aGupta U D1 aNatrajan M1 aKatoch V M1 aKatoch K1 aChauhan D S00aExpression of CXCL10 (IP-10) and CXCL11 (I-TAC) chemokines during Mycobacterium tuberculosis infection and immunoprophylaxis with Mycobacterium indicus pranii (Mw) in guinea pig. a11-70 v133 a

Mycobacterium indicus pranii (earlier known as Mycobacterium w) has been used as an immunmodulatory agent in leprosy and tuberculosis by mediating the release of various cytokines and chemokines. CXCL10 (IP-10) and CXCL11 (I-TAC) chemokines are involved in T-cell migration and stimulation of natural killer cells in Mycobacterium tuberculosis infection. In this study, the effect of heat killed M. indicus pranii (alone and in conjunction with chemotherapy) on disease progression was determined by colony forming units (CFUs) in guinea pig lung following their aerosol infection and the expression levels of CXCL10 and CXCL11 were studied by quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) and in situ RT-PCR. Four groups of animals included; infection only (Rv), immunoprophylaxis (RvMw), chemotherapy (RvCh) and combination of immunoprophylaxis with chemotherapy (RvChMw). In the group where immunoprophylaxis was given in combination with chemotherapy, the CFU counts reduced significantly at 4th week post-infection as compared to animals that received immunoprophylaxis or chemotherapy alone. At the same time, all groups of animals had elevated expression of CXCL 10 which was significantly high only in animals that received Mw with or without chemotherapy. Unlike to CXCL 10, study demonstrated suppressed expression CXCL 11 in both immunoprophylaxis as well as chemotherapy groups that became up-regulated in synergistic response of immunoprophylaxis and chemotherapy. Taken together, data indicates that the expression of CXCL10 and CXCL11 positively correlates with anti-tubercular treatment (at least with combination of immunoprophylaxis and chemotherapy). Therefore, prior immunization with Mw appears to be a good immunomodulator for release of chemokines and augments the effect of chemotherapy.

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