Progesterone promotes CXCl2-dependent vaginal neutrophil killing by activating cervical resident macrophage-neutrophil crosstalk.

Vaginal infections in women of reproductive age represent a clinical dilemma with significant socioeconomic implications. The current understanding of mucosal immunity failure during early pathogenic invasions that allows the pathogen to grow and thrive is far from complete. Neutrophils infiltrate most tissues following circadian patterns as part of normal repair, regulation of microbiota, or immune surveillance and become more numerous after infection.

Compilation of regulations and procedures for monitoring filamentous fungi in hospital environments.

Air and surfaces in the hospital environment are a potential source of exposure to filamentous fungi (FF) that could cause invasive fungal diseases (IFD) in severely immunocompromised patients. The prevalent FF in IFD are species from the genera Aspergillus, Fusarium, Scedosporium, and those within the order Mucorales. We have compiled regulations and described the procedures used in the clinical mycology laboratory to assess the presence of FF in areas at risk for the development of IFD.

Vaginal neutrophil infiltration is contingent on ovarian cycle phase and independent of pathogen infection.

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial.

Vaginal neutrophils eliminate sperm by trogocytosis.

Study Question: What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm?

Summary Answer: We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs).

What Is Known Already: Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis.

Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Latin America (Argentina, Chile and Costa Rica): data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

Objectives: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Argentina, Chile and Costa Rica.

Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

Results: A total of 170 S.

Estradiol impairs epithelial CXCL1 gradient in the cervix to delay neutrophil transepithelial migration during insemination.

Female reproductive mucosa must allow allogenic sperm survival whereas at the same time, avoid pathogen infection. To preserve sperm from neutrophil attack, neutrophils disappear from the vagina during the ovulatory phase (high estradiol); although the mechanisms that regulate neutrophil influx to the vagina during insemination remain controversial. We investigated the sex hormone regulation of the neutrophil migration through the cervix during insemination and revealed that ovulatory estradiol dose fades the CXCL1 epithelial expression in the ectocervix and fornix; hence, retarding neutrophil migration and retaining them in the epithelium.

Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to .

Estradiol-based therapies predispose women to vaginal infections. Moreover, it has long been known that neutrophils are absent from the vaginal lumen during the ovulatory phase (high estradiol). However, the mechanisms that regulate neutrophil influx to the vagina remain unknown.

CCL20 Expression by Tumor-Associated Macrophages Predicts Progression of Human Primary Cutaneous Melanoma.

The chemokine axis CCR6/CCL20 is involved in cancer progression in a variety of tumors. Here, we show that CCR6 is expressed by melanoma cells. The CCR6 ligand, CCL20, induces migration and proliferation , and enhances tumor growth and metastasis Confocal analysis of melanoma tissues showed that CCR6 is expressed by tumor cells, whereas CCL20 is preferentially expressed by nontumoral cells in the stroma of certain tumors.

Evaluation of the potential therapeutic benefits of macrophage reprogramming in multiple myeloma.

Tumor-associated macrophages (TAM) are important components of the multiple myeloma (MM) microenvironment that support malignant plasma cell survival and resistance to therapy. It has been proposed that macrophages (MØ) retain the capacity to change in response to stimuli that can restore their antitumor functions. Here, we investigated several approaches to reprogram MØ as a novel therapeutic strategy in MM.

A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.

To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells.

Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients.

Estradiol-based contraceptives and hormonal replacement therapy predispose women to Candida albicans infections. Moreover, during the ovulatory phase (high estradiol), neutrophil numbers decrease in the vaginal lumen and increase during the luteal phase (high progesterone). Vaginal secretions contain chemokines that drive neutrophil migration into the lumen.

[Evaluation of mass spectrometry: MALDI-TOF MS for fast and reliable yeast identification].

The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique known as MALDI-TOF MS is a tool used for the identification of clinical pathogens by generating a protein spectrum that is unique for a given species. In this study we assessed the identification of clinical yeast isolates by MALDI-TOF MS in a university hospital from Argentina and compared two procedures for protein extraction: a rapid method and a procedure based on the manufacturer's recommendations. A short protein extraction procedure was applied in 100 isolates and the rate of correct identification at genus and species level was 98.

Synthesis of new anionic carbosilane dendrimers via thiol-ene chemistry and their antiviral behaviour.

A synthetic strategy has been developed for the preparation of anionic carbosilane dendrimers bearing sulfonate or carboxylate groups at their periphery by means of thiol-ene chemistry. It offers significant advantages, such as milder reaction conditions, shorter reaction times and more facile purification methods, when compared with other synthetic protocols used previously, e.g.

Female sex hormones regulate the Th17 immune response to sperm and Candida albicans.

Study Question: What role do female sex hormones play in the antisperm immune response?

Summary Answer: We found that sperm induce a Th17 immune response and that estradiol down-regulates the antisperm Th17 response by dendritic cells.

What Is Known Already: Estradiol down-regulates the immune response to several pathogens and impairs the triggering of dendritic cell maturation by microbial products.

Study Design, Size, Duration: Ex vivo and in vivo murine models of vaginal infection with sperm and Candida albicans were used to study the induction of Th17 and its hormonal regulation.

Development of sulphated and naphthylsulphonated carbosilane dendrimers as topical microbicides to prevent HIV-1 sexual transmission.

Objectives: For the last 20 years, the idea of alternative prevention strategies based on the use of topical vaginally products to inhibit HIV-1 infection in women has been established. The concept of a 'microbicide' product has been born out of the unavailability of a vaccine against HIV-1 and the problems of women in negotiating the use of preventive prophylaxis by their partners, especially in developing countries.

Design: We have developed and evaluated polyanionic carbosilane dendrimers G3-S16 and G2-NF16 with sulphated and naphthylsulphonated end groups as nonspecific microbicides.

Estradiol downregulates NF-κb translocation by Ikbkg transcriptional repression in dendritic cells.

To reconcile immunity and reproduction, females must allow spermatozoa to survive and control the presence of commensal microbiota and sexually transmitted pathogens during ovulation. Female steroid sex hormones exert a powerful effect on the immune system, as do the hormonal changes associated with the ovarian cycle. Dendritic cells (DCs) are immunological sentinels that link innate immunity to adaptive immunity.

A new chimeric protein represses HIV-1 LTR-mediated expression by DNA methylase.

Once the human immunodeficiency virus (HIV) genome is inserted into the host genome, the virus cannot be removed, which results in latency periods and makes it difficult to eradicate. The majority of strategies to eradicate HIV have been based on preventing virus latency, thereby enabling antiretroviral drugs to act against HIV replication. Another innovative strategy is permanently silencing the integrated virus to prevent the spread of infection.

Mesenchymal contribution to recruitment, infiltration, and positioning of leukocytes in human melanoma tissues.

To understand factors that regulate leukocyte entry and positioning within human melanoma tissues, we performed a multiparametric quantitative analysis of two separated regions: the intratumoral area and the peritumoral stroma. Using two mesenchymal markers, fibroblast activation protein (FAP) and CD90, we identified three subsets of mesenchymal cells (MCs): (i) intratumoral FAP(+)CD90(low/-) MC, (ii) peritumoral FAP(+)CD90(+) MC, and (iii) FAP(-)CD90(+) perivascular MC. We characterized CD90(+) MCs, which showed a stable CCL2-secretory phenotype when long-term expanded ex vivo, and heavily surrounded peritumoral Duffy antigen receptor for chemokine(+) (DARC) postcapillary venules, supporting a role for these vessels in peritumoral inflammatory leukocyte recruitment.

The inhibition of Th17 immune response in vitro and in vivo by the carbosilane dendrimer 2G-NN16.

We evaluated the 2G-NN16-carbosilane dendrimer activities in Th17 response as a potential therapy for Th17 deregulated pathologies. IL17A, IL17F, IL22, IL23 and other interleukins secreted by Th17 cells CD4+ cells were down regulated when cells were cultured in the presence of this dendrimer. Furthermore, IL17F and IL17A protein levels in splenocytes from mice pretreated with 2G-NN16 dendrimer in a Th17 induction mouse model were lower than those corresponding to PBS treated mice.

pH-dependent interdomain tethers of CD1b regulate its antigen capture.

As CD1 proteins recycle between the cell surface and endosomes, they show altered receptiveness to lipid antigen loading. We hypothesized that changes in proton concentration encountered within distinct endosomal compartments influence the charge state of residues near the entrance to the CD1 groove and thereby control antigen loading. Molecular dynamic models identified flexible areas of the CD1b heavy chain in the superior and lateral walls of the A' pocket.

Combined inactivation of the Candida albicans GPR1 and TPS2 genes results in avirulence in a mouse model for systemic infection.

Inhibition of the biosynthesis of trehalose, a well-known stress protectant in pathogens, is an interesting approach for antifungal or antibacterial therapy. Deletion of TPS2, encoding trehalose-6-phosphate (T6P) phosphatase, results in strongly reduced virulence of Candida albicans due to accumulation of T6P instead of trehalose in response to stress. To further aggravate the deregulation in the pathogen, we have additionally deleted the GPR1 gene, encoding the nutrient receptor that activates the cyclic AMP-protein kinase A signaling pathway, which negatively regulates trehalose accumulation in yeasts.

Role of lipid trimming and CD1 groove size in cellular antigen presentation.

Cellular CD1 proteins bind lipids that differ in length (C(12-80)), including antigens that exceed the capacity of the CD1 groove. This could be accomplished by trimming lipids to a uniform length before loading or by inserting each lipid so that it penetrates the groove to a varying extent. New assays to detect antigen fragments generated within human dendritic cells showed that bacterial antigens remained intact, even after delivery to lysosomes, where control lipids were cleaved.

RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters.

The leukocyte integrins CD11a/CD18 (LFA-1, alphaLbeta2) and CD49d (VLA-4, alpha4beta1, alpha4beta7) mediate leukocyte transendothelial migration during immune and inflammatory responses and provides co-stimulatory signals for the activation of T lymphocytes. Our previous studies demonstrate that the CD11a gene promoter directs CD11a/CD18 integrin expression, and it depends on two overlapping sequences within the MS7 element, RUNX-110 and CEBP-100, which are recognized by RUNX and C/EBP transcription factor families, respectively. Recognition of MS7 differs in lymphoid (RUNX) and myeloid (C/EBP and RUNX) cells and its in vivo occupancy is regulated in a competitive and differentiation-dependent manner.

Regulated expression of the pathogen receptor dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin in THP-1 human leukemic cells, monocytes, and macrophages.

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and mediates binding and internalization of pathogens such as virus (human immunodeficiency virus, hepatitis C), bacteria (Mycobacterium), fungi, and parasites. DC-SIGN expression in vivo is primarily restricted to interstitial dendritic cells (DC) and certain tissue macrophages. We now report that leukemic THP-1 cells, widely used as a model for monocyte-macrophage differentiation, express very low basal levels of DC-SIGN and that DC-SIGN expression in THP-1 cells is regulated during differentiation.