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Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of M. tuberculosis. Cellular immunity has a pivotal role against M. tuberculosis infection, but the role of humoral immunity is still controversial. We analyzed the frequency, absolute counts, and phenotypic and functional subsets of B lymphocytes in the peripheral blood of patients with active TB and subjects with latent infection compared to healthy donors. Moreover, we analyzed serum levels of total Ig and their IgA, IgM, and IgG isotypes and the titers of preexisting antibodies against a pool of common viral pathogens. FlowCT and unsupervised clusterization analysis show that patients with active TB and LTBI subjects have modest non-significant reduction in the numbers of circulating B lymphocytes as compared to healthy donors. Moreover, LTBI subjects had high percentages of atypical B cell population and lower percentages of naive and switched memory B cells. These findings were supported by gene expression and GSEA analysis. Moreover, there were no differences between active TB patients, LTBI subjects and HD, either in serum levels of total Ig isotypes or in preexisting IgG antibody titers, to ten different antigens from eight common pathogenic viruses, clearly demonstrating that either active or latent M. tuberculosis infection preserves the antibody production capacity of long-lived plasma cells. Thus, our results agree with previous studies reporting unaltered B cell frequencies in the blood of active TB patients and LTBI individuals as compared to healthy controls.

The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases.Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as “memory”.T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8+TRMand TSCMcells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases.

Platelets regulate human inflammatory responses that lead to disease. However, the role of platelets in tuberculosis (TB) pathogenesis is still unclear. Here, we show that patients with active TB have a high number of platelets in peripheral blood and a low number of lymphocytes leading to a high platelets to lymphocytes ratio (PL ratio). Moreover, the serum concentration of different mediators promoting platelet differentiation or associated with platelet activation is increased in active TB. Immunohistochemistry analysis shows that platelets localise around the lung granuloma lesions in close contact with T lymphocytes and macrophages. Transcriptomic analysis of caseous tissue of human pulmonary TB granulomas, followed by Gene Ontology analysis, shows that 53 platelet activation-associated genes are highly expressed compared to the normal lung tissue. In vitro activated platelets (or their supernatants) inhibit BCG-induced T- lymphocyte proliferation and IFN-γ production. Likewise, platelets inhibit the growth of intracellular macrophages of Mycobacterium (M.) tuberculosis. Soluble factors released by activated platelets mediate both immunological and M. tuberculosis replication activities. Furthermore, proteomic and neutralisation studies (by mAbs) identify TGF-β and PF4 as the factors responsible for inhibiting T-cell response and enhancing the mycobactericidal activity of macrophages, respectively. Altogether these results highlight the importance of platelets in TB pathogenesis.