RESUMO
Mucosal immunity defines the relationship of surfaces in contact with the environment and integrates diverse tissues such as epidermis, gum, nose, gut, uterus and prostate with the immune system. Although considered part of a system, each mucosa presents specific immune features beyond the barrier and secretory functions. Information regarding the mucosal immunology of the male reproductive tract and the prostate gland in particular is scarce. In this review, we approach the prostate as an epithelial barrier and as part of the mucosal immune system. Finally, we also raise a series of questions that will improve the understanding of this gland, its role in reproduction and its sensitivity/resistance to disease.
Assuntos
Imunidade nas Mucosas , Próstata/imunologia , Infecções do Sistema Genital/imunologia , Sêmen/imunologia , Transdução de Sinais/imunologia , Animais , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Masculino , Proteínas NLR/metabolismo , Próstata/metabolismo , Próstata/microbiologia , Infecções do Sistema Genital/microbiologia , Sêmen/metabolismo , Receptores Toll-Like/metabolismoRESUMO
Mycoplasma genitalium was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. It is a sexually transmitted bacterium associated with a number of urogenital conditions in women like cervicitis, endometritis, pelvic inflammatory disease, infertility, and susceptibility to human immunodeficiency virus (HIV). However, M. genitalium may also act like a stealth pathogen at female reproductive tract, giving no symptoms. Its prevalence varies between different groups, with the average being 0.5-10% in the general population and 20-40% in women with sexually transmitted infections. The recommended treatment of this infection is azithromycin as a single 1-g dose. However, in recent years, macrolide resistance has increased which is significantly lowering the cure rate, being less than 50% in some studies. New treatment regimens need to be investigated due to increasing drug resistance. The discussion and suggestion of an algorithm for management of this infection is the highlight of this paper.
Assuntos
Farmacorresistência Bacteriana , Infecções por Mycoplasma/diagnóstico , Mycoplasma genitalium/patogenicidade , Infecções do Sistema Genital/microbiologia , Infecções Sexualmente Transmissíveis/microbiologia , Antibacterianos/uso terapêutico , Infecções Assintomáticas , Azitromicina/uso terapêutico , Feminino , Humanos , Macrolídeos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/isolamento & purificação , Doença Inflamatória Pélvica/microbiologia , Prevalência , Infecções do Sistema Genital/tratamento farmacológico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Uretrite/microbiologiaRESUMO
A significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with Chlamydia trachomatis, which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protective immune response is mediated by CD4+ Th1 cytokine responses. Herein, we demonstrate that early after infecting the male genital tract, C. muridarum triggers the production of IL-10 by splenic and lymph node cells. In addition, C. muridarum triggers IL-6 and TNFα secretion. Data obtained from in vitro and in vivo experiments revealed B cells as the major IL-10 contributors. Indeed, purified B cells produced high amounts of IL-10 and also exhibited enhanced expression of inhibitory molecules such as CD39, PD-L1 and PD1 after C. muridarum stimulation. In vitro experiments performed with sorted cell subsets revealed that Marginal Zone B cells were the main IL-10 producers. In vitro and in vivo studies using TLR-deficient mice indicated that TLR4 signaling pathway was essential for IL-10 production. In addition, in vivo treatments to neutralize IL-10 or deplete B cells indicated that IL-10 and B cells played a significant role in delaying bacterial clearance ability. Moreover, the latter was confirmed by adoptive cell transfer experiments in which the absence of IL-10-producing B cells conferred the host a greater capability to induce Th1 responses and clear the infection. Interestingly, NOD mice, which were the least efficient in clearing the infection, presented much more Marginal Zone B counts and also enhanced TLR4 expression on Marginal Zone B cells when compared to B6 and BALB/c mice. Besides, treatment with antibodies that selectively deplete Marginal Zone B cells rendered mice more capable of inducing enhanced IFNγ responses and clearing the infection. Our findings suggest that B cells play a detrimental role in C. muridarum infection and that activation by innate receptors like TLR4 and IL-10 production by these cells could be used by Chlamydia spp. as a strategy to modulate the immune response establishing chronic infections in susceptible hosts.
Assuntos
Linfócitos B/imunologia , Infecções por Chlamydia/imunologia , Chlamydia muridarum/genética , Genitália Masculina/microbiologia , Interleucina-10/metabolismo , Infecções do Sistema Genital/microbiologia , Linfócitos T/imunologia , Transferência Adotiva/métodos , Animais , Infecções por Chlamydia/microbiologia , Técnicas de Inativação de Genes , Interleucina-10/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Reação em Cadeia da Polimerase em Tempo Real , Infecções do Sistema Genital/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Escherichia coli is a natural colonizer of the urogenital mucosa of healthy females; however it is one of the pathogens associated to reproductive failures in cows and sows. A better knowledge about the characteristics of native E. coli will allow us to differentiate them from pathogenic strains. Ninety autochthonous isolates from the reproductive tract of sows and cows were characterized to determine the phylogenetic profile, antibiotic resistance and virulence factors; also, comparisons between different breeding systems were performed. Vaginal colonization of E. coli was statistically higher in cows (57.5%) than sows (23.8%), and most isolates belonged to the phylogenetic group A: 79.69 and 80.77%, respectively; moreover phylo-groups B1 (12.5 and 11.54%) and D (7.81 and 7.69%) were significantly lower; however, none was classified as B2. Positive associations between virulence factors and group D were found. Isolates with antimicrobial susceptibility were associated with group A and the MDR (Multiple Drug Resistance) was related to the porcine source. These results contribute to the knowledge of extra-intestinal E. coli populations; which could affect the reproductive performance of females.
Assuntos
Doenças dos Bovinos/microbiologia , Infecções por Escherichia coli/veterinária , Infecções do Sistema Genital/veterinária , Doenças dos Ovinos/microbiologia , Animais , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Microbiota , Infecções do Sistema Genital/tratamento farmacológico , Infecções do Sistema Genital/microbiologia , Ovinos , Doenças dos Ovinos/tratamento farmacológico , SuínosAssuntos
Micetoma/diagnóstico por imagem , Nocardiose/diagnóstico por imagem , Nocardia/isolamento & purificação , Ovário/diagnóstico por imagem , Doença Inflamatória Pélvica/diagnóstico por imagem , Infecções do Sistema Genital/diagnóstico por imagem , Dor Aguda/etiologia , Dor Aguda/prevenção & controle , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Dor nas Costas/etiologia , Dor nas Costas/prevenção & controle , Diagnóstico Diferencial , Monitoramento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Micetoma/tratamento farmacológico , Micetoma/microbiologia , Micetoma/patologia , Nocardia/efeitos dos fármacos , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Nocardiose/patologia , Ovário/efeitos dos fármacos , Ovário/microbiologia , Ovário/patologia , Doença Inflamatória Pélvica/tratamento farmacológico , Doença Inflamatória Pélvica/microbiologia , Doença Inflamatória Pélvica/patologia , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Infecções do Sistema Genital/tratamento farmacológico , Infecções do Sistema Genital/microbiologia , Infecções do Sistema Genital/patologia , Resultado do Tratamento , Redução de Peso , Adulto JovemRESUMO
La mucosa vaginal ha sido utilizada largamente para la administración de antimicrobianos destinados al tratamiento de infecciones endógenas del tracto genital inferior (IETGI) en mujeres embarazadas y no embarazadas. Candida spp elabora biopelículas (BP) y su formación es un proceso complejo que requiere que las células fúngicas establezcan múltiples interacciones con el medio. Las BP están rodeadas por un exopolímero (EPM) que puede restringir la actividad de anticuerpos, la difusión de sustancias y unirse a los antimicrobianos (AM), limitando su acción. Los antimicrobianos (AM) en general y los antimicóticos en particular (AMC) pueden tener dificultades para llegar a las células dentro del EPS. Muchas de las fórmulas que se emplean para el tratamiento empírico usan combinaciones inapropiadas con limitada o nula actividad sobre las biopelículas (BP). La presencia de moléculas que provoquen su inhibición anulando los inductores del EPM o por otro mecanismo, permitirá la actividad del AM específico. Objetivo: demostrar que la actividad de la clindamicina (CLI) en fórmula dual con ketoconazol (KET) actúa sobre BP Candida albicans (CA) y especies no albicans de Candida . (NAC). Métodos: estudiamos la actividad de clindamicina-ketoconazol (CK) sobre la adherencia y dispersión de BP de 8 aislamientos vaginales de CA y 7 de CNA. Se inocularon en 3 tubos con caldo Sabouraud y un dispositivo de vidrio para la formación de la BP según técnica ya descrita. Adherencia: Se incubaron durante 6 horas y se agregó una combinación de CK proveniente del material de óvulos, diluido convenientemente (62,5/260,4 ug/ml), a uno de los tubos de cada aislamiento tomándose como hora 0. Dispersión: esa misma dilución se agregó a otro tubo a las 16 horas. El tercer tubo quedó como testigo sin antimicrobianos. La lectura se efectuó con microscopio óptico a las 24 horas de agregada la combinación CK previa tinción con cristal violeta y se evaluaron con programas fotográficos. Por separado analizamos la actividad de CLI (62,5 ug/ml) y KET (260,4 ug/ml) con técnica similar. Seleccionamos las muestras de 7 pacientes que demostraron candidiasis vulvovaginal (CVV) y las estudiamos con la técnica de capas celulares. Se empleó la combinacion CK para el estudio de la adherencia y dispersión. Resultados: Adherencia se demostró poca influencia de CK en la adherencia con respecto a cada testigo. Dispersión: la influencia de CK se demostró en la mayoría de los aislamientos particularmente en los de CNA que mostraron una mayor presencia de EPM. Las hifas solo se observaron en 1/15 de los aislamientos de Candida spp cuando se agregó CK a las 16 horas. En las BP de las muestras clínicas no aparecieron hifas ni otro elemento micótico en 5/7 con respecto a los testigos. Conclusión: Según estos resultados el uso de una combinación de CK en BP de Candida spp, resulta en una adecuada penetración del AMC demostrada por la dispersión de la BP al cabo de 24 horas. Clindamicina no interfiere con la acción del ketoconazol sino que promovería su actividad anti-candida modificando posiblemente estructuras de superficie y la del EP por inhibición de las moléculas que facilitan la expresión del mismo. In vivo promueve la actividad inmunomoduladora que no se puede demostrar con este modelo in vitro. Su uso combinado en fórmulas duales facilitaría la actividad del AMC sobre Candida spp actuando como inhibidora o modificadora de las BP mediante la dispersión del EPM
The vaginal mucosa has been widely used for administering antimicrobial agents to treat endogenous infections of the lower genital tract in pregnant and non-pregnant women. Candida spp. elaborates biofilms, and its formation is a complex process requiring that fungal cells establish multiple interactions with the medium. Biofilms are surrounded by an exopolymer matrix that can restrict the activity of antibodies, the diffusion of substances, and be associated with antimicrobials, therefore limiting its actions. General antimicrobials and particular anti-mycotic agents can face difficulties to access the cells within the exopolymer matrix. Many formulas used for empirical treatment have improper combinations with limited or null activity on the biofilms. The presence of molecules that cause its inhibition, thus eliminating the exopolymer matrix inducers, or by other mechanism, will allow the specific antimicrobial activity. Objective: To show that the activity of clindamycin used in dual formula with ketoconazole works on Candida albicans biofilm and on non- albicans species of Candida . Methods: We studied the activity of clindamycin and ketoconazole regarding the adherence and dispersion of biofilms from eight vaginal isolates of C. albicans and 7 of non- albicans Candida . The isolates were inoculated in three tubes with Sabouraud agar and a glass device to form the biofilm according to a known technique. Adherence : Each isolate was incubated for a six-hour period and a combination of clindamycin and ketoconazole from the material of ovules was added and conveniently diluted to one of the tubes of each isolate (62.5/260.4 ug/mL), considering 0 hour. Dispersion: The same dilution was added to another tube after 16 hours. The third tube was used as a control without antimicrobials. The reading was carried out with an optical microscope after 24 hours that the clindamycin and ketoconazole combination had been added and colored with crystal violet. They were then evaluated using photographic programs. The activity of clindamycin (62.5 ug/mL) and ketoconazole (260.4 ug/mL) was analyzed alone with a similar technique. We chose vaginal samples from seven patients with vulvovaginal candidiasis and studied them through the cell layer technique. The clindamycin and ketoconazole combination was used for studying the adherence and dispersion. Results: Adherence: Little influence of clindamycin and ketoconazole was seen in adherence regarding each control. Dispersion: The clindamycin and ketoconazole influence was seen in most of the isolates, especially in those of non- albicans Candida that showed higher presence of exopolymer matrix . The hyphae were only seen in 1 of 15 isolates of Candida spp after the clindamycin and ketoconazole were added at the 16th hour. In biofilms of clinical samples, neither hyphae nor mycotic elements were seen in 5 of 7 compared with the controls. Conclusion: According to these results, the use of a clindamycin and ketoconazole combination in biofilms of Candida spp results in proper penetration of the antimicrobial agent, which is seen by the biofilm dispersion during 24 hours. Clindamycin does not interfere with the action of ketoconazole, but it would promote its anti- Candida activity and would possibly modify surface and EP structures through inhibition of the molecules that facilitate its expression. The in vivo model promotes the immunomodulatory activity that in vitro models do not. Its combined use in dual formulas would facilitate the antimicrobial activity on Candida spp, therefore working as an inhibitor or modifier of the biofilms after dispersion of the exopolymer matrix
Assuntos
Humanos , Feminino , Candidíase Vulvovaginal/microbiologia , Clindamicina/farmacologia , Cetoconazol/farmacologia , Infecções do Sistema Genital/microbiologiaRESUMO
The microbial community of the reproductive appara-tus, when known, can provide information about the health of the host. Metagenomics has been used to characterize and obtain genetic infor-mation about microbial communities in various environments and can relate certain diseases with changes in this community composition. In this study, samples of vaginal surface mucosal secretions were col-lected from five healthy cows and five cows that showed symptoms of reproductive disorders. Following high-throughput sequencing of the isolated microbial DNA, data were processed using the Mothur soft-ware to remove low-quality sequences and chimeras, and released to the Ribosomal Database Project for classification of operational taxo-nomic units (OTUs). Local BLASTn was performed and results were loaded into the MEGAN program for viewing profiles and taxonomic microbial attributes. The control profile comprised a total of 15 taxa, with Bacteroides, Enterobacteriaceae, and Victivallis comprising the highest representation of OTUs; the reproductive disorder-positive profile comprised 68 taxa, with Bacteroides, Enterobacteriaceae, His-tophilus, Victivallis, Alistipes, and Coriobacteriaceae being the taxa with the most OTU representation. A change was observed in both the community composition as well as in the microbial attributes of the profiles, suggesting that a relationship might exist between the patho-gen and representative taxa, reflecting the production of metabolites to disease progression.
Assuntos
Bactérias/genética , Microbiota/genética , Infecções do Sistema Genital/microbiologia , Vagina/microbiologia , Animais , Bactérias/classificação , Bactérias/patogenicidade , Bovinos , Feminino , Metagenômica , Filogenia , RNA Ribossômico 16S/genética , Infecções do Sistema Genital/veterináriaRESUMO
Microorganisms in the pregnant female genital tract are not always associated with pathology. The factors that influence the maternal response to microorganisms remain ill defined. We review the state of knowledge of microbe-host interactions in gestational tissues and highlight mechanisms that promote tolerance or pathogenesis. Tolerance to microorganisms is promoted during pregnancy by several mechanisms including upregulation of anti-inflammatory mediators, induction of endotoxin tolerance, and possibly by regulation of autophagy. Conversely, an altered vaginal microbiota or a pre-existing viral presence may result in induction of excessive inflammation and preterm labor. Although infections play a prevalent role in preterm birth, microbes are present in gestational tissues of women with healthy outcomes and may provide beneficial functions. The complex interactions between different microbial species and the maternal immune system during gestation remain incompletely elucidated.
Assuntos
Genitália Feminina/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Nascimento Prematuro/microbiologia , Infecções do Sistema Genital/microbiologia , Feminino , Humanos , GravidezRESUMO
To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Mutação de Sentido Incorreto , Infecções por Mycoplasma/microbiologia , Mycoplasma hominis/efeitos dos fármacos , Infecções do Sistema Genital/microbiologia , DNA Girase/genética , DNA Topoisomerase IV/genética , Humanos , Mycoplasma hominis/genética , Mycoplasma hominis/isolamento & purificaçãoRESUMO
The aim of this work was to evaluate the effects of beneficial human vaginal lactobacilli (Lb) on urogenital pathogens through in vitro and in vivo experiments. Co-aggregative and antimicrobial properties between five vaginal Lb strains and urogenital pathogens or potential pathogens (Streptococcus agalactiae, Staphylococcus aureus and Candida albicans strains) were assayed. Also, associative cultures of Lb strains and S. agalactiae were performed and bacterial growth, pH, lactic acid and hydrogen peroxide (H2O2) were determined at different times. Based on the results obtained, the in vivo studies were assayed in mice with Lactobacillus gasseri CRL 1509 or Lactobacillus salivarius CRL 1328 inoculated intravaginally (i.v.) and then challenged i.v. with S. agalactiae. Results were analysed by ANOVA (repeated measures and general linear models). Most of the Lb strains increased the percentage of aggregation of S. agalactiae strains. Only one strain (Lactobacillus reuteri CRL 1324) positively affected the aggregation of S. aureus and none increased the aggregation of C. albicans. The inhibition of the growth of S. agalactiae strains by production of organic acids by lactobacilli was evidenced. The Lb-S. agalactiae co-cultures showed a significant inhibition of the pathogen after 4 h and 8 h of incubation. Parallel increases in lactic acid and H2O2 levels were observed. However, in the experimental murine model, no significant differences were obtained in the number of streptococci recovered from the vaginal tract of control mice and those inoculated with Lb. In conclusion, vaginal Lb exhibited in vitro co-aggregative and antimicrobial effects on S. agalactiae strains, suggesting that they could be promising candidates for protection against S. agalactiae challenge. However, as these effects were not evidenced in the murine model used, further animal studies under different experimental conditions should be conducted to evaluate the preventive effect of Lb against challenge with S. agalactiae.