Comparison of CD4+/CD8+ Lymphocytic Subpopulations Pre- and Post-Antituberculosis Treatment in Patients with Diabetes and Tuberculosis.

Is there a CD4+ and CD8+ immunity alteration in patients with pulmonary tuberculosis (TB) and diabetes (DM) that does not recover after antituberculosis treatment? This prospective comparative study evaluated CD4+ and CD8+ lymphocytic subpopulations and antituberculosis antibodies in patients with diabetes and tuberculosis (TB-DM), before and after antituberculosis treatment. CD4+ T cell counts were lower in patients with TB-DM compared to those with only TB or only DM, and these levels remained low even after two months of anti-TB treatment. Regarding the CD8+ T cell analysis, we identified higher blood values in the DM-only group, which may be explained by the high prevalence of latent tuberculosis (LTBI) in patients with DM. IgM antituberculosis antibodies levels were elevated in patients with only TB at baseline, and 2 months post-anti-TB treatment, IgG did not express any relevant alterations. Our results suggest an alteration in CD4+ immunity in patients with TB-DM that did not normalize after antituberculosis treatment.

Necrosis, netosis, and apoptosis in pulmonary tuberculosis and type-2 diabetes mellitus. Clues from the patient's serum.

Pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (T2DM) are two inflammatory diseases whose pathology involves neutrophils (NEU) as key participants. Countless inflammatory elements produced at the lesion sites leak into the blood and are distributed systemically. The study aimed to investigate the effect of the serum of patients with PTB, T2DM, and PTB + T2DM on the cellular and nuclear morphology of healthy NEU. Monolayers of NEU were prepared and incubated with sera from PTB (n꓿ 10), T2DM (n꓿10), PTB + T2DM (n꓿ 10) patients, or sera from healthy people (n = 10). Monolayers were stained for histones, elastase, and myeloperoxidase for NETosis, annexin V for apoptosis, and Iris fuchsia for necrosis. Hoechst stain (DNA) was used to identify the nuclear alterations. Necrosis was the predominant alteration. Sera from PTB + T2DM were the most potent change inducers. Normal sera did not induce cell alterations. The blood of TBP and T2DM patients carries a myriad of abnormal elements that induce necrosis of NEU in normal people, thus reflecting what might occur in the neutrophils of the patients themselves. These findings reinforce the participation of NEU in the pathology of these diseases. Necrosis is expected to be the most frequent neutrophil-induced alteration in tuberculosis and diabetes mellitus.

Sera from patients with tuberculosis increase the phagocytic-microbicidal activity of human neutrophils, and ESAT-6 is implicated in the phenomenon.

Background: It has been reported that sera from patients with active pulmonary tuberculosis (APT) induced nuclear changes in normal neutrophils that included pyknosis, swelling, apoptosis, and production of extracellular traps (NETs). Similar changes were observed with some sera from their household contacts but not with sera from healthy, unrelated individuals. It was suggested that those sera from household contacts that induced neutrophil nuclear changes might correspond to people with subclinical tuberculosis. Thus, our experimental approach might serve to identify individuals with early, ongoing disease. Methods: Nuclear changes in neutrophils were fully evident by 3 h of contact and beyond. Circulating mycobacterial antigens were the most likely candidates for this effect. We wanted to know whether the nuclear changes induced on neutrophils by the sera of APT patients would negatively affect the phagocytic/microbicidal ability of neutrophils exposed to APT sera for short periods. Results: We now provide evidence that short-term contact (30 min) with sera from patients with pulmonary tuberculosis increases several phagocytic parameters of normal neutrophils, including endocytosis, myeloperoxidase levels, production of free reactive oxygen species, phagolysosome fusion, and microbicidal activity on Staphylococcus aureus, with these effects not being observed with sera from healthy donors. We also give evidence that suggests that ESAT-6 and CFP-10 are involved in the phenomenon. Conclusion: We conclude that activation is a stage that precedes lethal nuclear changes in neutrophils and suggests that autologous neutrophils must circulate in an altered state in the APT patients, thus contributing to the pathology of the disease.

Murine interferon-gamma inducible protein-10 (IP-10) secreted by Lactococcus lactis chemo-attracts human CD3+ lymphocytes.

Chemokines are members of the super family of cytokines necessary for leukocyte recruitment in tissues and lymphoid organs. The interferon-gamma inducible protein-10 (IP-10) chemo-attracts CXCR3-expressing cells, such as activated T lymphocytes and monocytes. We have genetically engineered a strain of Lactococcus lactis to secrete a biologically active murine IP-10 that interacts with human CXCR3, its homolog receptor, and chemo-attracts human CD3+ T lymphocytes.

Opportunistic intestinal parasites in immunocompromised patients from a tertiary hospital in Monterrey, Mexico.

Opportunistic parasites are still important agents causing morbidity and mortality in immunocompromised patients, particularly those living with HIV/AIDS. Few studies in Mexico have attempted to determine the prevalence of opportunistic intestinal parasites causing diarrhea in immunocompromised patients. A study was conducted to determine the intestinal parasites in HIV-positive and HIV-negative immunocompromised patients with diarrhea admitted to a tertiary care hospital in Monterrey, Mexico, from 2014 to 2015. Stool samples were examined for trophozoites, cysts, and eggs using the EGRoPe sedimentation-concentration technique and special techniques (modified Ziehl-Neelsen stain, modified trichrome stain). A total of 56 patients were included. The overall prevalence of intestinal parasitism was 64% (36/56); 22/36 patients were HIV-positive. Prevalence of opportunistic parasites was 69% in HIV-infected patients compared to 44% in HIV-negative patients (P = 0.06). Microsporidia were the most frequently identified parasites (24/36, 67%), followed by Cryptosporidium sp. (6/36, 17%), Sarcocystis sp. (4/36, 11%), Cystoisospora belli (3/36, 8%), and Cyclospora cayetanensis (1/36, 3%). Overall prevalence rates of microsporidiosis and cryptosporidiosis were 43% and 11%, respectively. Among HIV-infected patients, prevalence rates of microsporidiosis and cryptosporidiosis were 48% and 14%, respectively. We also report the first cases of intestinal sarcocystosis in Mexico, all in HIV-infected patients. In conclusion, microsporidia and coccidia are major parasitic agents causing diarrhea in immunocompromised patients, particularly HIV-infected patients.

Tuberculosis: mecanismos de defensa, inmunopatogénesis y biomarcadores de susceptibilidad y resistencia

La TB, una enfermedad infectocontagiosa, continúa siendo un problema de salud mundial. Los mecanismos de defensa del huésped contra esta bacteria se encuentran sobre todo en las vías respiratorias altas y bajas. Sus principales componentes son la lisozima, la lactoferrina, las defensinas, las catelicidinas y las proteínas surfactantes. La interacción de Mtb, con receptores en los macrófagos que reconocen patrones moleculares, favorece la internalización de la micobacteria y la producción de citocinas. Las citocinas proinflamatorias, como IL-1, TNF-a e IL-6 y la quimiocina IL-8, juegan un papel importante en el proceso inflamatorio inicial en la infección. IL- 12 y citocinas de origen Th1, como IFN-g y el FAM (factor activador de macrófagos), son importantes en la activación de linfocitos y del macrófago durante el proceso de resolución de la infección. La regulación del proceso inflamatorio por citocinas, como IL-10, TGFb e IL-4, es importante para la sobrevivencia intracelular del microorganismo, pero ésta debe darse en un balance para evitar la supresión del sistema inmune contra Mtb. La búsqueda de biomarcadores de susceptibilidad y resistencia se ha ampliado en la TB pulmonar, principalmente enfocados a moléculas del complejo mayor de histocompatibilidad y a los receptores de componentes bacterianos que permiten su internalización. Es importante revisar estos aspectos, para entender mejor la inmunopatogenia de la TB y porqué todavía en nuestros tiempos sigue siendo una enfermedad difícil de erradicar.