Reduced Th17 Response in Patients with Tuberculosis Correlates with IL-6R Expression on CD4⁺T Cells

Abstract

Our results demonstrate that reduced Th17 responses were associated with the clinical outcome of M. tuberculosis infection. Suppression of Th17 response through down-regulation of IL-6R expression may be an important mechanism in the development of active TB.

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

“…The inhibition of an M. tuberculosis-specific response has been associated with the bacterial load and the severity of the disease (11,32,53). In concordance with these studies, we found an inverse relationship between the frequency of IFN-␥-producing cells and the severity of the disease as measured by the AFB smear, although it did not reach statistical significance.…”

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria

“…Previous studies reported lower mycobacteria-specific cytokineproducing peripheral blood Th17 CD4 1 T cells in TB patients compared with persons with latent TB infection. Furthermore, patients with severe TB had significantly lower Th17 response than those with mild disease (36). However, there are limited data on IL-17 in the alveolar compartment because previous studies were hampered by difficulties in detecting alveolar Th17 cells because of their very low frequencies (37) and low concentrations of IL-17 in diluted BAL fluid (38).…”

Vaccine-Induced Th17 Cells Are Maintained Long-Term Postvaccination as a Distinct and Phenotypically Stable Memory Subset

“…Although Th17 cells have been found to be dispensable for overall protection against mycobacterial infections (4,25), IL-17-producing ␥␦-T cells do play a certain role in shaping innate and adaptive responses leading to granuloma formation (57), whereas classical (␣␤ CD4 ϩ ) Th17 cells have been associated with early and IFN-␥-independent protection (54). In humans, long-lived Ag-specific Th17 cells with a central memory phenotype and distinct from Th1 have been identified in PBMCs from healthy, mycobacterium-exposed individuals and from individuals with latent tuberculosis infection, whereas significantly reduced Th17 responses were found in patients with active TB (6,46). This correlation, with lower Th17 responses and disease progression, was not due to relocation to the lungs, as Th17 responses were found to be low to undetectable in bronchoalveolar lavage fluid and in pleural effusion from TB patients, possibly reflecting infection-mediated Th17 downregulation (6,43,46).…”

“…In humans, long-lived Ag-specific Th17 cells with a central memory phenotype and distinct from Th1 have been identified in PBMCs from healthy, mycobacterium-exposed individuals and from individuals with latent tuberculosis infection, whereas significantly reduced Th17 responses were found in patients with active TB (6,46). This correlation, with lower Th17 responses and disease progression, was not due to relocation to the lungs, as Th17 responses were found to be low to undetectable in bronchoalveolar lavage fluid and in pleural effusion from TB patients, possibly reflecting infection-mediated Th17 downregulation (6,43,46). However, since their discovery (20,41) it has become clear that exaggerated and uncontrolled Th17 responses can be associated with autoimmunity and pathological conditions (7,9,14).…”