ANALYSIS OF THE POTENTIAL PREDICTIVE POSSIBILITY OF CELL EXTRACTION MARKERS AS THE HELD INDICATORS OF TREATMENT ANTI-TB IN PATIENTS WITH ACTIVE LUNG TUBERCULOSIS
Name: BRUNA SOUSA DE MENDONÇA PORTELA
Publication date: 01/07/2016
Advisor:
Name |
Role |
|---|---|
| DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| CARLOS EDUARDO TADOKORO | External Examiner * |
| DANIEL CLAUDIO DE OLIVEIRA GOMES | Advisor * |
| MOISES PALACI | Internal Alternate * |
| RICARDO PINTO SCHUENCK | External Alternate * |
| RODRIGO RIBEIRO RODRIGUES | Internal Examiner * |
Summary: Tuberculosis (TB) infection caused by Mycobacterium tuberculosis (Mtb) continues to represent a serious risk to public health. Current treatment routines require long period of care and also are toxic, which often lead to low adhesion and increase of multidrug-resistant strains. Infectious processes that result in antigen persistence or even chronic
inflammatory syndromes affect the effector function of antigen-specific T cells reducing its ability to proliferate and to produce inflammatory mediators and develop the cytotoxic functions. The phenomenon described as cell exhaustion, which is characterized by a high expression of PD-1, TIM-3, CTLA-4 and KLRG-1 receptors has
been described as the main mechanism involved in this immune deactivation. In addition, the severity of infections caused by pathogens such as HIV, HBV and HCV are correlated with increased expression of these markers, which suggest their association in the pathogenesis and also indicate a potential target as predictive
marker of immunologic/therapeutic efficacy. In this work we aimed to evaluate the expression of the cell exhaustion receptors PD-1 and TIM-3 as a potential target for therapeutic efficacy during chemotherapy against active pulmonary Tuberculosis. We showed higher frequencies of PD-1 and TIM-3 in patients with TB and the consequent loss the expression after treatment initiation. Moreover, we observed an significant increase of IFN-ɣ and decreased IL-10 production, which directly reflected on the microbicidal capacity observed in the whole blook killing assay. Additionally a positive
correlation between TIM3+ and PD1+TIM3+ expression in CD8 T cell and bacillary load was observed indicating a possible association of this receptor to clinical evolution. Our results extend the knowledge for development of new strategies in predictive diagnosis and therapeutic efficacy for TB, which may be exploited to elimination of tuberculosis.
