title: Intracellular survival of Mycobacterium tuberculosis in macrophages is modulated by phenotype of the pathogen and immune status of the host.
abstract: Emerging evidence indicates that the causative agent of tuberculosis is more genetically and functionally diverse than appreciated previously. The impact of this variation on the clinical manifestation of the disease remains largely unknown. In addition, there exists significant variability in the immune status of the host governing susceptibility to tuberculosis. The effect of these variations on the host pathogen interaction was investigated by taking varying pathogen phenotypes (virulent H37Rv, a-virulent H37Ra and a multidrug resistant strain #591) and varying host (18 MDR-TB and 16 fresh TB patients and 10 healthy, BCG-vaccinated individuals). The key question was whether the intracellular survival of Mycobacterium tuberculosis (MTB) in human monocyte-derived macrophages (MDM), an attribute of pathogenic potential, can be modulated by the immune status of the hosts or phenotype of MTB. The findings of this study indicate that induction of TNF-α may not be a global indicator of virulence of a strain. TNF-α release may be differentially regulated in response to the same strain depending upon the immune status of the host. Moreover, the phenotype of the infecting MTB and the host's immune status played a comparable role in the intracellular survival of MTB. This picture supports the hypothesis that in addition to the phenotype variation of the mycobacteria, the immune status of an individual will greatly influence the outcome of the host-pathogen interaction. These results may have a bearing on the future endeavors in vaccine development and TB control strategy.
authors.affiliation: Department of Microbiology, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: Monika_sharma18@rediffmail.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Microbiology, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: mridulabose@hotmail.com.
authors.forename: Mridula
authors.initials: M
authors.lastname: Bose
authors.affiliation: Department of Microbiology, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: mannu.abhimanyu1986@gmail.com.
authors.lastname: Abhimanyu
authors.affiliation: Department of Microbiology, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: drlatikasharma@gmail.com.
authors.forename: Latika
authors.initials: L
authors.lastname: Sharma
authors.affiliation: Department of Respiratory Medicine, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: dramitdiwakar@gmail.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Diwakar
authors.affiliation: Department of Microbiology, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: sujeet13@hotmail.com.
authors.forename: Sujeet
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Respiratory Medicine, Vallabhbhai Patel Chest Institute, New Delhi, India. Electronic address: SNGaur@yahoo.com.
authors.forename: Shailendra Nath
authors.initials: SN
authors.lastname: Gaur
authors.affiliation: Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, Kingsway Camp, New Delhi, India. Electronic address: jnbanavaliker@yahoo.com.
authors.forename: Jayant Nagesh
authors.initials: JN
authors.lastname: Banavalikar
keywords: Host variation; IL-12; Monocyte-derived macrophages; Nitric oxide; Pathogen variation; TNF-α