Abstract
Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), γδ T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a (p = 0.025), NKp80 (p = 0.033), and NKG2C (p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2–24). A higher frequency of the γδ T cell population was observed in the TB/HIV patients with inversion of the Vδ2+/Vδ2− ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular γδ T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and γδ T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6–24). An increase of CD161+ NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients.
Highlights
Tuberculosis (TB) is one of the world’s deadliest diseases and affects ∼10.0 million people worldwide
immune reconstitution inflammatory syndrome (IRIS) has been associated with lower CD4+ T cell counts at combined antiretroviral therapy (cART) initiation followed by a dramatic improvement in these cell counts and a rapid plasma viral load decay that lead to partial restoration of overall immune functions, and the presence of opportunistic pathogens [8,9,10,11]; the immunopathogenesis of this syndrome and the major clinical and laboratory factors associated with IRIS onset are not clearly understood [12]
Among the 33 TB/HIV recruited participants, only 4 (12.1%) developed symptoms consistent with IRIS after beginning cART, which was in agreement with the frequency of IRIS observed in our previous studies [28, 45]
Summary
Tuberculosis (TB) is one of the world’s deadliest diseases and affects ∼10.0 million people worldwide. A total of 9.4% of these cases occurred in the city of Rio de Janeiro, which is ranked as the second Brazilian state capital in terms of the number of TB/HIV cases and is considered a TB-endemic region [3,4,5]. IRIS has been associated with lower CD4+ T cell counts at cART initiation followed by a dramatic improvement in these cell counts and a rapid plasma viral load decay that lead to partial restoration of overall immune functions, and the presence of opportunistic pathogens [8,9,10,11]; the immunopathogenesis of this syndrome and the major clinical and laboratory factors associated with IRIS onset are not clearly understood [12]. In a previous study by our group, an increase in immune responses was observed in TB/HIV IRIS patients compared with those of non-IRIS patients, as was a marked increase in IFN-γ production by T cells from IRIS patients in response to PPD and other Mtb antigens [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
