Trichomonas vaginalis causes trichomoniasis, an inflammatory process related to an increased rate of HIV transmission. In order to study T. vaginalis infection response in a microorganism-free ...environment, an infection model was established providing a host–parasite interaction system useful to study the interplay between immune cells and the parasite. Infected mice peritoneal cells were immunophenotyped at different times after infection using flow cytometry. Neutrophils and macrophages showed the most relevant increase from third to 12th day post-infection. A high number of B lymphocytes were present on 15th day post-infection, and an increase in memory T cells was observed on sixth day post-infection. The levels of NO increased at day 10 post-infection; no significant influence was observed on T. vaginalis clearance. Increased viability of T. vaginalis was observed when the NETs inhibitors, metformin and Cl− amidine, were administrated, highlighting the importance of this mechanism to control parasite infection (43 and 86%, respectively). This report presents a comprehensive cell count of the immune cells participating against trichomoniasis in an in vivo interaction system. These data highlight the relevance of innate mechanisms such as specific population changes of innate immune cells and their impact on the T. vaginalis viability.
Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and ...noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.
Highlights • Evaluation of surface and soluble TREM-1 levels in DENV-infected patients was made. • A significant reduction of TREM-1 expression was observed in neutrophils. • Sera from DENV-infected ...patients exhibited significantly higher of soluble TREM-1 levels during the first 5 days after the symptoms onset. • The increment of sTREM-1 could be a compensatory mechanism to counteract the inflammatory process elicited by DENV infection. • These data are the first to show the involvement of TREM-1 during DENV infection.
Summary
Inflammation is necessary for survival, but it is also an important cause of human morbidity and mortality, as exemplified by sepsis. During inflammation, cells of the innate immune system ...are recruited and activated in response to infection, trauma or injury. These cells are activated through receptors, such as Toll‐like receptors (TLRs), which recognize microbial ligands such as lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)‐1 amplifies the inflammatory response initiated by TLRs, and its expression on the surface of monocytes increases in the presence of TLR ligands. Here we have shown that in monocytes TREM‐1 mRNA levels, measured by reverse transcription–polymerase chain reaction (RT–PCR), remained unchanged and TREM‐1 protein levels, measured by flow cytometry, increased, indicating that LPS increases TREM‐1 expression by a post‐transcriptional mechanism. We also showed that TREM‐1/Fc fusion protein decreased the ability of the sera of some patients with sepsis to activate monocytes, indicating that the TREM‐1 ligand, whose identity is unknown, may be present in the sera of some of these patients. We describe a mechanism for the regulation of TREM‐1 expression on monocytes and the possible presence of its ligand in serum; these findings help to explain the contribution of TREM‐1 during systemic inflammation.
Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain “maternal-fetal ...tolerance”, SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.
A rapid increase in the tyrosine phosphorylation of signal transducer and activators of transcription (STAT) proteins has been extensively documented in cells stimulated with cytokines and growth ...factors, but virtually nothing is known about the regulation of STAT5 activation in breast cancer cells stimulated with basement membrane (BM) components. Stimulation of MCF7 cells with type IV collagen (Col-IV) promoted a striking increase in the phosphorylation of STAT5 at Tyr-694, as revealed by site-specific antibodies that recognized the phosphorylated state of this residue. In addition, Col-IV also stimulated STAT5 nuclear translocation and an increased in STAT5 DNA binding activity. Treatment with the selective Src family inhibitor pyrazolopyrimidine PP-2 prevented STAT5 phosphorylation at Tyr-694, nuclear translocation of STAT5 and the STAT5-DNA complex formation. Our results demonstrate, for the first time, that stimulation with Col-IV induces STAT5 phosphorylation of endogenous STAT5 at Tyr-694, nuclear translocation of STAT5 and increases in STAT5 DNA binding activity via a Src-dependent pathway in MCF7 cells.
Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates ...regulatory T (Treg) cells are still unknown. Our goal was to determine whether PRL plays a role in Treg function. We measured the expression of PRL and its receptor in Treg and effector T (Teff) cells from 15 healthy individuals. We also evaluated the functional activity of Treg cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that Treg cells constitutively expressed PRL receptor, whereas Teff cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by Treg cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of Treg and Teff cells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in Treg cells but not in Teff cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of Treg cells, apparently through the induced secretion of Th1 cytokines.
Inflammation is necessary for survival, but it is also an important cause of human morbidity and mortality, as exemplified by sepsis. During inflammation, cells of the innate immune system are ...recruited and activated in response to infection, trauma or injury. These cells are activated through receptors, such as Toll-like receptors (TLRs), which recognize microbial ligands such as lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)-1 amplifies the inflammatory response initiated by TLRs, and its expression on the surface of monocytes increases in the presence of TLR ligands. Here we have shown that in monocytes TREM-1 mRNA levels, measured by reverse transcription-polymerase chain reaction (RT-PCR), remained unchanged and TREM-1 protein levels, measured by flow cytometry, increased, indicating that LPS increases TREM-1 expression by a post-transcriptional mechanism. We also showed that TREM-1-Fc fusion protein decreased the ability of the sera of some patients with sepsis to activate monocytes, indicating that the TREM-1 ligand, whose identity is unknown, may be present in the sera of some of these patients. We describe a mechanism for the regulation of TREM-1 expression on monocytes and the possible presence of its ligand in serum; these findings help to explain the contribution of TREM-1 during systemic inflammation.
Human pregnancy disorders such as preeclampsia are thought to involve variations in cytokine levels. It has been proposed that, in preeclamptic women, a balance favoring the Th1-type over the ...Th2-type cytokine profile determines local or systemic immunologic responses to pregnancy and that this may cause defective placental implantation and placental ischemia, which activate systemic endothelial cells. The purpose of this study was to determine whether cytokine expression differs in the maternal, choriodecidual, and fetal compartments, and between women with or without preeclampsia.
Plasma concentrations of interferon gamma (IFNgamma), interleukin (IL)-2, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) in samples obtained from maternal peripheral blood (MPB), choriodecidual (CD), and fetal cord (FC) blood compartments of 17 women with preeclampsia and in 15 normotensive women. Intracellular concentrations of IFNgamma and IL-2 in T lymphocytes were assessed by flow cytometry.
Plasma IFNgamma concentrations in both MPB and CD compartments were significantly higher in preeclamptic than in normotensive women. Maternal plasma IL-4 concentration was significantly lower in preeclamptic than in normotensive women. Intracellular IFNgamma and IL-2 concentrations did not differ significantly between preeclamptic and normotensive women.
The dominant Th1-type over Th2-type cytokine profile is evident in MPB, but not in the CD and FC blood compartments. This might reflect the complex cytokine networks in the fetal-placental interface and might involve trophoblasts or decidual and endothelial cells, which could account for the increased plasma IFNgamma concentration and T-helper cell number.
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