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Understanding the immune response to Leishmania infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of Leishmania infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (TRM), play a crucial role in concomitant immunity against cutaneous Leishmania infections. These TRM cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4+ TRM cells, in particular, have been implicated in protection against Leishmania infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-g, which activates macrophages to kill parasites. The induction of CD4+ TRM cells has shown promise in experimental immunization, leading to protection against Leishmania challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4+ TRM cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that Leishmania-specific memory CD4+ Tcell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4+ TRM cell populations. Overall, this review highlights the importance of memory T cells, particularly skinresident CD4+ TRM cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: Zoonotic Cutaneous Leishmaniasis is increasing in the world and Phlebotomus papatasi as a proven vector was considered in different aspects for disease control. Sandfly saliva contains proteins which provoke host immune system. These proteins are candidates for developing vaccines. Objectives: The main purpose of this research was comparing evaluation of salivary glands proteomes from wild P. papatasi. Extracting these proteins and purifying of original SP15 as inducer agent in vector salivary glands from endemic leishmaniasis foci were other objectives. Methods: Adult sandflies were sampled using aspirators and funnel traps from three endemic foci in 2017–2018. Each pair of salivary glands of unfed females was dissected and proteins were extracted using thermal shocking and sonication methods. Purification was performed through RP‐HPLC. All equivalent fractions were added together in order to reach sufficient protein concentration. Protein content and profile determination were examined with SDS‐PAGE. Results: The protein concentration of whole‐salivary glands of specimens was determined approximately 1.6 µg/µl (Isfahan) and 1 µg/µl (Varamin and Kashan). SDS‐PAGE revealed 10 distinct bands between 10 and 63 kDa. Analysis of proteomes showed some similarities and differences in the chromatograms of different foci. SDS‐PAGE of all collected fractions revealed SP15‐like proteins were isolated in 24 min from Varamin, 26 to 30 min from Kashan and 29.4 min from Isfahan and were around 15 kDa. Conclusions: Isolation of salivary components of Iranian wild P. papatasi is very important for finding potential proteins in vaccine development and measuring control strategy of zoonotic cutaneous leishmaniasis in Iran and this could be concluded elsewhere in the world. [ABSTRACT FROM AUTHOR]

Abstract: Recovery from CL is usually accompanied with long-lasting protection and induction of strong immune response. The phenotypes, generation and maintenance of central (=TCM) and effector (=TEM) memory T cell subsets in human leishmaniasis are not well known. Profile of T cell subsets were analyzed on peripheral CD8+ T cells from volunteers with history of cutaneous leishmaniasis (HCL). In HCL and control groups, mean frequencies of CCR7+CD45RA+CD8+ naïve and CCR7−CD45RA−CD8+ TEM cells were higher than other subsets before culture, but after stimulation with soluble Leishmania antigen, the frequency of naïve T cells was significantly decreased and the frequency of TEM cells was significantly increased. TEM phenotype composed the highest portion of proliferating Carboxy Fluorescein diacetate Succinimidyl Ester (CFSE)-dim population which was significantly higher in HCL volunteers than in control group. Stimulation of isolated CD8+ memory T cells, but not naïve T cells, from HCL volunteers induced a significantly higher IFN-γ production compared with that of healthy controls. Intracellular IFN-γ staining provided the same result. Memory population is shown to be responsible for Leishmania-induced IFN-γ production. Leishmania-reactive proliferating TEM cells were identified as the most frequent subset which may play a role in recall immune response and protection against Leishmania infection. [Copyright &y& Elsevier]

Background: In human leishmaniasis Th1/Th2 dichotomy similar to murine model is not clearly defined and surrogate marker(s) of protection is not yet known. In this study, Th1/Th2 cytokines (IL-5, IL-10, IL-13 and IFN-γ) profile induced by purified CD4+/CD8+ T cells in response to Leishmania antigens were assessed at transcript and protein levels in 14 volunteers with a history of self-healing cutaneous leishmaniasis (HCL) and compared with 18 healthy control volunteers. Methodology/Principal Findings: CD4+/CD8+/CD14+ cells were purified from peripheral blood using magnetic beads; CD4+/CD8+ T cells were co-cultured with autologous CD14+ monocytes in the presence of soluble Leishmania antigens (SLA). Stimulation of either CD4+ T cells or CD8+ T cells of HCL volunteers with SLA induced a significantly (P<0.05) higher IFN-γ production compared with the cells of controls. Upregulation of IFN-γ gene expression in CD4+ cells (P<0.001) and CD8+ cells (P = 0.006) of HCL volunteers was significantly more than that of controls. Significantly (P<0.05) higher fold-expression of IFN-γ gene was seen in CD4+ cells than in CD8+ cells. In HCL volunteers a significantly (P = 0.014) higher number of CD4+ cells were positive for intracellular IFN-γ production than CD8+ cells. Conclusions/Significance: Collectively, the volunteers have shown maintenance of specific long-term immune responses characterized by a strong reaction to leishmanin skin test and IFN-γ production. The dominant IFN-γ response was the result of expansion of both CD4+ and CD8+ T cells. The results suggested that immune response in protected individuals with a history of zoonotic cutaneous leishmaniasis (ZCL) due to L. major is mediated not only through the expansion of antigen-specific IFN-γ producing CD4+ Th1 cells, but also through IFN-γ producing CD8+ T cells. Author Summary: Cutaneous leishmaniasis (CL) is usually a self-healing skin lesion caused by different species of Leishmania parasite. Resistance and susceptibility of mice to Leishmania major infection is associated with two types of CD4+ T lymphocytes development: Th1 type response with production of cytokine IFN-γ is associated with resistance, whereas Th2 type response with production of cytokines IL-4 and IL-5 is associated with susceptibility. A clear Th1/Th2 dichotomy similar to murine model is not defined in human leishmaniasis and we need as much information as possible to define marker(s) of protection. We purified CD4+/CD8+ T cells, stimulated them with Leishmania antigens and analysed gene and protein expression of Th1/Th2 cytokines in volunteers with a history of self-healing CL who are presumed to be protected against further Leishmania infection. We have seen significant upregulation of IFN-γ gene expression and high IFN-γ production in the Leishmania stimulated CD4+ T cells and CD8+ T cells. We concluded that both antigen-specific IFN-γ producing CD4+ Th1 cells and IFN-γ producing CD8+ T cells contribute to the long term protection in individuals with a history of CL. This proves the importance of CD8+ T cells as a source of IFN-γ in Th1-like immune responses. [ABSTRACT FROM AUTHOR]

Background: Trichomonas vaginalis ( T.vaginalis ) and Neisseria gonorrhoeae ( N.gonorrhoeae ) are two most common non-viral sexually transmitted infections in the world. No data are available regarding the epidemiology of genital infections in women of Qom, central Iran., Objective: Epidemiological investigation of sexually transmitted infections in genital specimens of women referred to the referral gynecology hospital in Qom, central Iran., Materials and Methods: Genital swab specimens were collected from women volunteers and used for identification of bacterial and protozoal infections by conventional microbial diagnostics, porA pseudo gene LightCycler ® real-time PCR (for N.gonorrhoeae ) and ITS-PCR (for T.vaginalis )., Results: Of 420 volunteers, 277 (65.9%) had genital signs/symptoms, including 38.3% malodorous discharge, 37.9% dyspareunia, and 54.8% abdominal pain. Totally, 2 isolates of Streptococcus agalactiae were identified. Five specimens (1.2%) in Thayer-Martin culture and 17 (4.1%) in real-time PCR were identified as N.gonorrhoeae . Fifty-four specimens (12.9%) in wet mount, 64 (15.2%) in Dorset's culture, and 81 (19.3%) in ITS-PCR showed positive results for T.vaginalis . Five mixed infections of T.vaginalis + N.gonorrhoeae were found. The risk of T.vaginalis infection was increased in women with low-birth-weight (p = 0.00; OR=43.29), history of abortion (p = 0.00; OR=91.84), and premature rupture of membranes (PROM) (p = 0.00; OR=21.75). The probability of finding nuclear leukocytes (p = 0.00; OR=43.34) in vaginal smear was higher in T.vaginalis infection., Conclusion: The significant prevalence of trichomoniasis and gonorrhea emphasizes the need for accurate diagnosis and effective surveillance to prevent serious reproductive complications in women., Competing Interests: Authors declare they have no conflict of interests.

Background: Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Early detection and treatment of C.trachomatis genital infection prevent serious reproductive complications., Objective: Performances of enzyme immunoassay (EIA) and major outer membrane protein (MOMP)-polymerase chain reaction (PCR) for diagnosis of genital C.trachomatis infection in women were compared., Materials and Methods: In this cross sectional study a total of 518 women volunteers were included (33.67±8.3 yrs) who had been referred to Gynecology clinics of Qom province, Iran, were included. Endocervical swab specimens were collected to detect lipopolysaccharide (LPS) antigen in EIA and to amplify MOMP gene of C.trachomatis in PCR. Results were confirmed using ompI nested-PCR. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated for performance of the tests. Odds ratios were determined using binary logistic regression analysis., Results: In total, 37 (7.14%) cases were positive by EIA and/or MOMP-PCR. All discrepant results were confirmed by nested-PCR. Sensitivity, specificity, PPV and NPV values of EIA were 59.46%, 100%, 100% and 96.98%, and those of MOMP-PCR were 97.30%, 100%, 100%, 99.79%, respectively. Reproductive complications including 2.7% ectopic pregnancy, 5.4% stillbirth, 5.4% infertility, and 10.8% PROM were recorded. The risk of developing chlamydiosis was increased 4.8-fold in volunteers with cervicitis (p<0.05; OR 4.80; 95% CI 1.25-18.48)., Conclusion: C.trachomatis infection should be regarded in women of reproductive ages especially those with cervicitis. Primary screening of women by using the low cost antigen-EIA is recommended; however, due to the low sensitivity of Ag-EIA, verification of the negative results by a DNA amplification method is needed.