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Background: Persistent respiratory symptoms and lung abnormalities post‐COVID‐19 are public health problems. This study evaluated biomarkers to stratify high‐risk patients to the development or persistence of post‐COVID‐19 interstitial lung disease. Methods: One hundred eighteen patients discharged with residual lung abnormalities compatible with interstitial lung disease (COVID‐ILD patients) after a severe COVID‐19 were followed for 1 year (post‐COVID‐ILD patients). Physical examination, pulmonary function tests, and chest high‐resolution computed tomography (HRCT) were performed. Soluble forms (s) of PD‐L1, PD‐L2, TIM‐3, and GAL‐9 were evaluated in serum and cell culture supernatant, as well as T‐cells subsets and the transmembrane expression of PD‐L1 and PD‐L2 on the cell surface. Results: Eighty percent of the post‐COVID‐ILD patients normalized their lung function at 1‐year follow‐up, 8% presented COVID‐independent ILD, and 12% still showed functional and HRCT alterations. PD‐L2 levels were heterogeneous during acute COVID‐19 (aCOVID); patients who increased (at least 30%) their sPD‐L2 levels at 1 year post‐COVID‐19 and exhibited altered CD4/CD8 ratio showed persistence of chest tomographic and functional alterations. By contrast, patients who decreased sPD‐L2 displayed a complete lung recovery. sPD‐L1, sTIM‐3, and sGAL‐9 increased significantly during aCOVID and decreased in all patients after 1‐year follow‐up. Conclusion: Increased sPD‐L2 and an altered CD4/CD8 ratio after 12 months of aCOVID are associated with the persistence of lung lesions, suggesting that they may contribute to lung damage post‐COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (M.tb). B cells are the central mediator of the humoral response; they are responsible for producing antibodies in addition to mediating other functions. The role of the cellular response during the TB spectrum by B cells is still controversial. Methods: In this study, we evaluated the distribution of the circulating B cell subsets in patients with active and latent TB (ATB and LTB, respectively) and how they respond to stimuli of protein or lipid from M.tb. Results: Here, we show that ATB patients show an immune fingerprinting. However, patients with drug-sensitive- (DS-TB) or drug-resistant- (DR-TB) TB have altered frequencies of circulating B cells. DS-TB and DR-TB display a unique profile characterized by high systemic levels of IFN-γ, IL-10, IgG, IgG/IgM ratio, and total B cells. Moreover, B cells from DR-TB are less efficient in producing IL-10, and both DS-TB and DR-TB produce less IFN-γ in response to M.tb antigens. Conclusion: These results provide new insights into the population dynamics of the cellular immune response by B cells against M. tb and suggest a fingerprinting to characterize the B-cell response on DR-TB. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a public health problem worldwide and is one of the deadliest infectious diseases, only after the current COVID-19 pandemic. Despite significant advances in the TB field, there needs to be more immune response comprehension; for instance, the role played by humoral immunity is still controversial. This study aimed to identify the frequency and function of B1 and immature/transitional B cells in patients with active and latent TB (ATB and LTB, respectively). Here we show that LTB patients have an increased frequency of CD5+ B cells and decreased CD10+ B cells. Furthermore, LTB patients stimulated with mycobacteria's antigens increase the frequency of IFN-γ-producing B cells, whereas cells from ATB do not respond. Moreover, under the mycobacterial protein stimulus, LTB promotes a pro-inflammatory environment characterized by a high level of IFN-γ but also can produce IL-10. Regarding the ATB group, they cannot produce IFN-γ, and mycobacterial lipids and proteins stimulate only the IL-10 production. Finally, our data showed that in ATB, but not in LTB, B cell subsets correlate with clinical and laboratory parameters, suggesting that these CD5+ and CD10+ B cell subpopulations have the potential to be biomarkers to differentiate between LTB and ATB. In conclusion, LTB has increased CD5+ B cells, and these cells can maintain a rich microenvironment of IFN-γ, IL-10, and IL-4. In contrast, ATB only maintains an anti-inflammatory environment when stimulated with mycobacterial proteins or lipids. [ABSTRACT FROM AUTHOR]

Introduction: High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with Severe Immune Reconstitution Inflammatory Syndrome (Severe-IRIS-KS), which can occur after initiating cART, and leads to high mortality, particularly in patients with pulmonary involvement. We investigate if valganciclovir (as an anti-HHV-8 agent) initiated before cART reduces the mortality associated with Severe-IRIS-KS and the incidence of Severe-IRIS-KS. Methods: Open-label parallel-group randomized clinical trial in AIDS cART naïve patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node, or gastrointestinal involvement, lymphedema, or ≥30 skin lesions. In the experimental group (EG), patients received valganciclovir 900 mg BID four weeks before cART and continued until week 48; in the control group (CG), cART was initiated on week 0. Non-severe-IRIS-KS was defined as: an increase in the number of lesions plus a decrease of ≥one log10 HIV-VL, or an increase of ≥50cells/mm3 or ≥2-fold in baseline CD4+cells. Severe-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia. Results: 40 patients were randomized and 37 completed the study. In the ITT analysis, at 48 weeks, total mortality was the same in both groups (3/20), severe-IRIS-KS attributable mortality was 0/20 in the EG, compared with 3/20 in the CG (p = 0.09), similar to the per-protocol analysis: 0/18 in the EG, and 3/19 in the control group (p = 0.09). The crude incidence rate of severe-IRIS-KS was four patients developed a total of 12 episodes of Severe-IRIS-KS in the CG and two patients developed one episode each in the EG. Mortality in patients with pulmonary KS was nil in the EG (0/5) compared with 3/4 in the CG (P = 0.048). No difference was found between groups in the number of non-S-IRIS-KS events. Among survivors at week 48, 82% achieved >80% remission. Conclusions: Although mortality attributable to KS was lower in the EG the difference was not statistically significant. [ABSTRACT FROM AUTHOR]

Introduction: T cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD-1) are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim-3 and PD-1 is induced after chronic antigen-specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim-3 with its ligand galectin-9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim-3 expression profile before and after six months of antiretroviralf therapy and the impact of Tim-3 and PD-1 blocking on immunity against M. tuberculosis. Materials and methods: HIV+ patients naive to anti-retroviral therapy (ART) were followed up for six months. Peripheral immune-cell phenotype (CD38/HLA-DR/galectin-9/Tim-3 and PD-1) was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array) by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis-infected macrophages were cultured with T cells in the presence or absence of Tim-3 and PD-1 blocking antibodies. Interleukin-1 beta treatment of infected macrophages was evaluated by enumerating colony-forming units. Results: We showed that HIV+ patients had an increased expression of Tim-3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim-3 and PD-1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. Conclusions: In this study, we demonstrated that increased Tim-3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and the in vitro manipulation of the Tim-3 and PD-1 molecules restored the functionality of Tcells and macrophages to restrict bacterial growth. Our results provide a novel immune strategy that may be implemented in the near future in order to improve the immune responses in HIV+ patients. Keywords: HIV; tuberculosis; Tim-3; galectin 9; PD-1., Introduction Pulmonary tuberculosis (TB) is one of the most important causes of death from infectious disease around the world. It is the leading cause of opportunistic infection and mortality among [...]

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments. [ABSTRACT FROM AUTHOR]