Variation in Gamma Interferon Responses to Different Infecting Strains of Mycobacterium tuberculosis in Acid-Fast Bacillus Smear-Positive Patients and Household Contacts in Antananarivo, Madagascar

Abstract

The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-␥) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-␥ production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major cause of global morbidity and mortality throughout the world. It is estimated that there are in excess of new 8 million cases of TB each year, and this represents just the tip of the iceberg. Infection with M. tuberculosis leads to clinically active TB in about 5 to 10% of exposed individuals. A much higher proportion of exposed individuals apparently become latently infected, and these individuals may remain noninfectious and symptom free for years. Approximately one-third of the world population is thought to be latently infected with M. tuberculosis. However, under some circumstances (in about 5% of the latently infected people), the host immune response is perturbed and latent M. tuberculosis infection may develop into clinically active TB (52). This process is most prominent in individuals coinfected with human immunodeficiency virus (HIV), but it can also occur with impairment of the immune system associated with old age, malnutrition, anti-inflammatory drug treatment, etc. Reactivation of latent disease is thought to contribute roughly half of all TB cases, and thus, understanding the factors controlling the development of acute primary TB or latent infection is crucial to TB control (64).Gamma interferon (IFN-␥) production has been widely used to study infection and to examine the human immune response to specific M. tuberculosis antigens. The 6-kDa early secreted antigenic target (ESAT-6) antigen, encoded by genes located within region of difference 1 (RD1) of the M. tuberculosis genome, is much more specific for M. tuberculosis than purified protein derivative (PPD), as these genes were deleted from M. bovis in the development of BCG substrains or are not found in most environmental mycobacteria (29,53). Some studies showed that the level of IFN-␥ release in response to ESAT-6 could identify TB contacts at risk of developing active disease after recent infection (3,18,30). CFP7 or TB10.4 is an immunodominant antigen recognized by TB patients and M. bovis BCG-vaccinated subjects, while ESAT-6 is specific to TB pa-

Modern lineages of <i>Mycobacterium tuberculosis</i> in Addis Ababa, Ethiopia: implications for the tuberculosis control programe

“…All the strains which are highly prevailed in Ethiopia (T, CAS, H, LAM and Beijing) are all members of the modern lineage and several studies showed that an immune response difference between isolates belonging to ''modern'' lineages with isolates belonging to ''ancient'' lineages. Recent studies have described a reduced immune response to Beijing and other modern strains and their association with rapid progression to severe disease, MDR and XDR tuberculosis in humans and experimental animals [17][18][19][20] .…”

Reduced Frequency of Memory T Cells and Increased Th17 Responses in Patients with Active Tuberculosis

“…The clinical heterogeneity of ATB as shown by the AFB sputum results ranging from 1ϩ to 3ϩ may explain the high variability found in the specific response to CFP-10 and PPD in this group. Additionally, the time of exposure of TB contacts to the index case (16,68) and the M. tuberculosis strains infecting the patients may also impact the IFN-␥ response (54).…”

Diversity and Evolution of Mycobacterium tuberculosis: Moving to Whole-Genome-Based Approaches

“…There is increasing evidence that this genomic diversity may influence important pathobiological properties, such as the transmissibility and virulence of the MTBC strains, as well as the immune responses and clinical pictures that they evoke (reviewed in Gagneux and Small 2007). Such an influence has been indicated by field studies looking at epidemiological or clinical correlates of transmissibility and virulence of strains from different lineages (e.g., de Jong et al 2006de Jong et al , 2008Kong et al 2007;Caws et al 2008;Rakotosamimanana et al 2010) or by detecting lineage-specific differences in virulence-related features, mycobacterial transcriptomic responses, or cytokine induction patterns in animal or cellular infection models (Lopez et al 2003;Homolka et al 2010;Portevin et al 2011;Reiling et al 2013).…”