Impaired TNF, IL-1β, and IL-17 production and increased susceptibility to Mycobacterium tuberculosis infection in HTLV-1 infected individuals

Background:

IFN-$\gamma$ and TNF play critical roles in the control of Mycobacterium tuberculosis (Mtb) infection. Despite leading to an exaggerated production of inflammatory cytokines, individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) have an increased risk of developing tuberculosis (TB). The specific immune mechanisms that explain this increased susceptibility, particularly regarding the production of cytokines other than IFN-$\gamma$, are not fully understood.

Abstract:

Methods: This case-control study compared the immune response to Mtb antigens in 36 HTLV-1 infected individuals (without TB) and 35 healthy controls (HC). Levels of TNF, IL-1$\beta$, IL-6, IL-10, IL-17, and IFN-$\gamma$ were measured in supernatants of whole blood cultures stimulated with Mtb antigens (ESAT-6/CFP-10). Additionally, the frequency of TST (tuberculin skin test) positivity was evaluated in 143 HTLV-1 patients compared to 143 controls.

Results: HTLV-1 infected individuals showed a significantly higher frequency of TST positivity compared to controls ($32.2\%$ vs. $13.3\%$, $P < .001$). While IFN-$\gamma$ production was similar between groups, HTLV-1 individuals had significantly lower levels of TNF ($P = .003$), IL-1$\beta$ ($P = .015$), and IL-17 ($P = .002$) in response to Mtb antigens compared to HC.

Conclusion: HTLV-1 infection impairs the production of key cytokines (TNF, IL-1$\beta$, and IL-17) necessary for containing Mtb, despite maintaining IFN-$\gamma$ levels. This specific defect in the innate and Th17 response likely explains the increased susceptibility and worse clinical outcomes of TB in HTLV-1 infected patients.

Keywords: HTLV-1; Tuberculosis; Co-infection; Immune response.

Clique aqui

• Data de Publicação: 03/01/2018
• Autores: Natália B. Carvalhoa , Maria de Lourdes Bastosa , Anselmo S. Souzaa , Eduardo M. Nettob,c , Sérgio Arrudad , Silvane B. Santosa,e,f , Edgar M. Carvalhoa,d,f,∗