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.

This study aimed to identify the distinct intrinsic response potential of γδ T cells from COVID-19 patients with different illness severities, to better understand the implication of these cells in COVID-19 disease. Forty-four COVID patients were enrolled at hospitalization and classified as: moderate without oxygen support (MWO₂; N = 15), moderate with oxygen support (MO₂; N = 15), or severe disease requiring mechanical ventilation (SD; N = 14). γδ T cells were characterized ex vivo, isolated from peripheral blood cells, stimulated in vitro with OKT3 and K562 cells, and evaluated for functional markers by flow cytometry. Ex vivo analysis identified 16.21% of total γδ T cells as Vδ1⁻Vδ2⁻. SD patients presented a lower frequency of TRAIL⁺ and of IL-17-producing Vδ2 cells, as well as lower value of fluorescence intensity values for TNF-α in Vδ2 cells, than MWO₂ patients (p < 0.05). In addition, paired analyses showed a lower frequency of IL-17-producing than CD161⁺ Vδ2 cells in SD patients (p < 0.05). These observations suggest a more restricted response potential of the Vδ2 subset in severe disease, show the impact of general immune dysregulation on these cells, or even suggest some role for IL-17-producing Vδ2 cells in preventing critical symptoms.

COVID-19 perturbs the renin-angiotensin system (RAAS) and inflammatory pathways, shaping disease severity. Soluble ACE2 (sACE2) and angiotensin II (Ang II) are central regulators of vascular and immune homeostasis. We profiled plasma from COVID-19 patients and controls using ELISA, together with 48 cytokine profiling and clinical data. Both sACE2 and Ang II were significantly elevated in patients. Increased Ang II was associated with oxygen supplementation and dyspnea, and negatively correlated with IL-3, whereas sACE2 correlated with IL-13 and FGF. Comorbidities modulated cytokine expression: diabetes mellitus was linked to reduced LIF and MCP-1, hypertension to decreased LIF and increased IP-10, and obesity to elevated IL-12p70. Age correlated with TNF and HGF, and reduced oxygen saturation was associated with lower LIF. These findings reveal that acute COVID-19 disrupts RAAS and amplifies immune dysregulation, with Ang II emerging as a pivotal mediator of respiratory compromise and inflammatory imbalance, underscoring its potential as a biomarker and therapeutic relevance.