Dual role of immune cells in the testis: protective or pathogenic for germ cells?

The purpose of this review is to describe how the immune cells present in the testis interact with the germinal epithelium contributing to survival or apoptosis of germ cells (GCs). Physiologically, the immunosuppressor testicular microenvironment protects GCs from immune attack, whereas in inflammatory conditions, tolerance is disrupted and immune cells and their mediators respond to GC self antigens, inducing damage of the germinal epithelium. Considering that experimental models of autoimmune orchitis have clarified the local immune mechanisms by which protection of the testis is compromised, we described the following topics in the testis of normal and orchitic rats: (1) cell adhesion molecule expression of seminiferous tubule specialized junctions and modulation of blood-testis barrier permeability by cytokines (2) phenotypic and functional characteristics of testicular dendritic cells, macrophages, effector and regulatory T cells and mast cells and (3) effects of pro-inflammatory cytokines (TNF-α, IL-6 and FasL) and the nitric oxide-nitric oxide synthase system on GC apoptosis.Fil: Pérez, Cecilia Valeria. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Theas, Maria Susana. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Jacobo, Patricia Verónica. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Jarazo Dietrich, Sabrina Soledad. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Guazzone, Vanesa Anabella. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Lustig, Livia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

Mycobacterium phlei cell wall complex directly induces apoptosis in human bladder cancer cells

Intact mycobacteria and mycobacterial cell wall extracts have been shown to inhibit the growth of human and murine bladder cancer. Their mechanism of action is, however, poorly understood. Mycobacterium phlei mycobacterial cell complex (MCC) is a cell wall preparation that has mycobacterial DNA in the form of short oligonucleotides complexed on the cell wall surface. In this study, we have investigated the possibility that MCC has anti-cancer activity that is mediated by two different mechanisms – a direct effect on cancer cell proliferation and viability and an indirect effect mediated by the production of interleukin 12 (IL-12), a cytokine known to possess anti-cancer activity. We have found that, although MCC is a potent inducer of IL-12 and IL-6 synthesis in monocytes and macrophages either in vitro or in vivo, it is unable to induce the synthesis of either IL-12, IL-6 or granulocyte–macrophage colony-stimulating factor (GM-CSF) by the human transitional bladder cancer cell lines HT-1197 and HT-1376. MCC is not directly cytotoxic towards these cancer cells, but induces apoptosis as determined by nuclear DNA fragmentation and by the release of nuclear mitotic apparatus protein. Mycobacterium phlei DNA associated with MCC is responsible for the induction of apoptosis. Our results indicate that MCC directly effects bladder cancer cells by inhibiting cellular proliferation through the induction of apoptosis, and has the potential for an indirect anti-cancer activity by stimulating cancer-infiltrating monocytes/macrophages to synthesize IL-12. © 1999 Cancer Research Campaig

Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells

Semen is the main vector for HIV-1 dissemination worldwide. It contains three major sources of infectious virus: free virions, infected leukocytes, and spermatozoa-associated virions. We focused on the interaction of HIV-1 with human spermatozoa and dendritic cells (DCs). We report that heparan sulfate is expressed in spermatozoa and plays an important role in the capture of HIV-1. Spermatozoa-attached virus is efficiently transmitted to DCs, macrophages, and T cells. Interaction of spermatozoa with DCs not only leads to the transmission of HIV-1 and the internalization of the spermatozoa but also results in the phenotypic maturation of DCs and the production of IL-10 but not IL-12p70. At low values of extracellular pH (∼6.5 pH units), similar to those found in the vaginal mucosa after sexual intercourse, the binding of HIV-1 to the spermatozoa and the consequent transmission of HIV-1 to DCs were strongly enhanced. Our observations support the notion that far from being a passive carrier, spermatozoa acting in concert with DCs might affect the early course of sexual transmission of HIV-1 infection

The value of misoprostol administration before intrauterine contraceptive device insertion: a systematic review and meta-analysis

Abstract Objectives To assess the value of misoprostol administration before IUD insertion. Search strategy Screening of PubMed, Scopus, Web Of Science, ScienceDirect, and clinical trials registry till April 2024 using the keywords misoprostol, prostaglandin E1 analogue, IUD, IUCD, intrauterine device, IUD insertion, and their MeSH terms. Selection criteria All RCTs that included misoprostol administration before IUD insertion. All doses, routes, and times of administration of misoprostol compared to placebo, analgesics, or other prostaglandins were included. This review included 19 RCTs including 2743 women (1333 had misoprostol administration and 1410 comparators (1281 received placebo, 16 received diclofenac, 43 received dinoglandin, and 70 received lignocaine). Data collection and analysis The extracted data included location setting, number of participants randomized and analyzed, participants selection criteria, the exact intervention details (including misoprostol dose, route and timing of administration, the comparator group details, and type of IUD inserted), primary and secondary outcomes of the trial ( including pain score, easiness of insertion score, the need for analgesics, the need for additional measures as cervical dilatation, failure of insertion, complications of the insertions process, and drug side effects), risk of bias of the included studies, and trial registration number and site. Main results Failure of IUD insertion was evaluated in 9 studies with 1350 participants and revealed an odd ratio (OR) of 0.87 with 0.39–1.98 95% CI, P value = 0.75, and I 2 score = 45%. The easiness score of insertion was evaluated in 7 studies with 780 participants and revealed an OR of − 1.12 with − 1.73 to 0.52 95% CI, P value < 0.001, and I 2 score = 87%. The pain VAS was evaluated in 13 studies with 1776 participants and revealed a mean difference (MD) of − 0.23 with − 0.77 to 0.31 95% CI, P value = 0.41, and I 2 score = 90%. The participants satisfaction score was evaluated in 3 studies with 366 participants and revealed a MD of 1.64 with 0.68–2.60 95% CI, P value < 0.001, and I 2 score = 91%. The need for analgesics and additional measures as cervical dilatation were evaluated in 7 and 4 studies with 813 and 295 participants respectively. The reported OR (95% CI), P values, and I 2 scores were 0.58 (0.32–1.03) and 0.79 (0.33–1.92), 0.06 and 0.61, and 48% and 35% respectively. Conclusion Misoprostol administration before IUD insertion was associated with higher easiness score, higher women satisfaction score, and higher side effects named nausea, vomiting, cramps, shivering, headache, and fever compared to placebo administration. Registration number CRD42022364291