Overproduction of inflammatory cytokines is a keystone event in COVID-19 pathogenesis; TNF and its receptors (TNFR1 and TNFR2) are critical pro-inflammatory molecules. ADAM17 releases the soluble (sol) forms of TNF, TNFR1, and TNFR2. This study evaluated TNF, TNFRs, and ADAM17 at the protein, transcriptional, and gene levels in COVID-19 patients with different levels of disease severity. In total, 102 patients were divided into mild, moderate, and severe condition groups. A group of healthy donors (HD; n = 25) was included. Our data showed that solTNFR1 and solTNFR2 were elevated among the COVID-19 patients (p < 0.0001), without increasing the transcriptional level. Only solTNFR1 was higher in the severe group as compared to the mildly ill (p < 0.01), and the level was higher in COVID-19 patients who died than those that survived (p < 0.0001). The solTNFR1 level had a discrete negative correlation with C-reactive protein (p = 0.006, Rho = −0.33). The solADAM17 level was higher in severe as compared to mild disease conditions (p < 0.01), as well as in COVID-19 patients who died as compared to those that survived (p < 0.001). Additionally, a potential association between polymorphism TNFRSF1A:rs767455 and a severe degree of disease was suggested. These data suggest that solTNFR1 and solADAM17 are increased in severe conditions. solTNFR1 should be considered a potential target in the development of new therapeutic options.

TNF and IFN-γ trigger cell damage during SARS CoV-2 infection; these cytokines can induce senescence and a cell death process called PANoptosis. This study included 138 vaccine-naïve COVID-19 patients, who were divided into four groups (Gp) according to the plasma level of TNF and IFN-γ (High [^Hi] or Normal-Low [^No-Low]), Gp 1: TNF^Hi/IFNγ^Hi; Gp 2: TNF^Hi/IFNγ^No-Low; Gp 3: TNF^No-Low/IFNγ^Hi; and Gp 4: TNF^No-Low/IFNγ^No-Low. Thirty-five apoptosis-related proteins and molecules related to cell death and senescence were evaluated. Our results showed that groups did not display differences in age and comorbidities. However, 81% of the Gp 1 patients had severe COVID-19, and 44% died. Notably, the p21/CDKN1A was increased in Gp 2 and Gp 3. Moreover, Gp 1 showed higher TNFR1, MLKL, RIPK1, NLRP3, Caspase 1, and HMGB-1 levels, suggesting elevated TNF and IFN-γ levels simultaneously activate diverse cell death pathways because it is not observed when only one of these cytokines is increased. Thus, high TNF/IFN-γ levels are predominant in severe COVID-19 status, and patients display cell alterations associated with the activation of diverse cell death pathways, including a possible senescent phenotype.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.

In mycobacterial infections, the number of cells from two newly discovered subpopulations of CD3⁺ myeloid cells are increased at the infection site; one type expresses the T cell receptor (CD3⁺TCRαβ⁺) and the other does not (CD3⁺TCRαβ⁻). The role of Mycobacterium tuberculosis (Mtb) virulence in generating these subpopulations and the ability of these cells to migrate remains unclear. In this study, monocyte-derived macrophages (MDMs) infected in vitro with either a virulent (H37Rv) or an avirulent (H37Ra) Mtb strain were phenotypically characterized based on three MDM phenotypes (CD3⁻, CD3⁺TCRαβ⁺, and CD3⁺TCRαβ⁻); then, their migration ability upon Mtb infection was evaluated. We found no differences in the frequency of CD3⁺ MDMs at 24 h of infection with either Mtb strain. However, H37Rv infection increased the frequency of CD3⁺TCRαβ⁺ MDMs at a multiplicity of infection of 1 and altered the expression of CD1b, CD1c, and TNF on the surface of cells from both the CD3⁺ MDM subpopulations; it also modified the expression of CCR2, CXCR1, and CCR7, thus affecting CCL2 and IL-8 levels. Moreover, H37Rv infection decreased the migration ability of the CD3⁻ MDMs, but not CD3⁺ MDMs. These results confirm that the CD3⁺ macrophage subpopulations express chemokine receptors that respond to chemoattractants, facilitating cell migration. Together, these data suggest that CD3⁺ MDMs are a functional subpopulation involved in the immune response against Mtb.

Early and accurate diagnoses of pathogenic microorganisms is essential to correctly identify diseases, treating infections, and tracking disease outbreaks associated with microbial infections, to develop precautionary measures that allow a fast and effective response in epidemics and pandemics, thus improving public health. Aptamers are a class of synthetic nucleic acid molecules with the potential to be used for medical purposes, since they can be directed towards any target molecule. Currently, the use of aptamers has increased because they are a useful tool in the detection of specific targets. We present a brief review of the use of aptamers to detect and identify bacteria or even some toxins with clinical importance. This work describes the advances in the technology of aptamers, with the purpose of providing knowledge to develop new aptamers for diagnoses and treatment of different diseases caused by infectious microorganisms.

The most commonly used toxins in biological warfare are staphylococcal enterotoxin B (3SEB), cholera toxin (1XTC), and botulinum toxin (3BTA). Uncovering novel strategies for identifying these toxins is paramount; therefore, aptamers are used for this purpose. Aptamers are single-stranded DNA or RNA oligonucleotides selected via Systematic Evolution of Ligands by Exponential Enrichment (SELEX) with high binding affinity and specificity against target molecules. However, SELEX in vitro is tedious; hence, adopting alternative in silico molecular docking approaches is necessary. We aimed to conduct molecular docking with accessible tools and obtain RNA aptamers. First, 4,820,095 sequences obtained from an initial library of 9.5 × 10⁹ Python script sequences were used. The GraphClust program was used to create representative groups or clusters, and the DoGSiteScorer (https://proteins.plus/) was used to conduct binding site detection of the proteins: 5DO4 (thrombin), 3SEB, 1XTC, and 3BTA. rDock, HDock, and PatchDock were adopted, combining different docking program results (consensus scoring), to improve receptor–ligand prediction. An analysis of the poses and root mean square deviation (RMSD) was performed, and 468 structurally different aptamers were obtained. The DoGSiteScorer program predicted the binding site of each protein to direct the interaction with the aptamer. Candidate aptamers for 3SEB, 1XTC, and 3BTA were selected according to the pose value considering the closeness of the interaction with a lower mean of 45.923 Å, 45.854 Å, and 72.490 Å, respectively. Communicated by Ramaswamy H. Sarma