A historical review of the role of cytokines involved in leishmaniasis.

Leishmaniasis is an infectious disease caused by the Leishmania genus, affecting millions of persons in the world. Despite increased studies, no vaccine has been developed against leishmaniasis, and drug resistance is evolving in some Leishmania species (spp). Innate and acquired immune cells and their associated cytokines interplay together to determine the immune responses related outcomes in leishmaniasis. Interferon (IFN)-γ or macrophage activating factor (MAF) is the first effective lymphokine (LK), with a related function to leishmaniasis, discovered in 1979. This review article discussed the history of cytokines involved in Leishmania infection, and it is the first report demonstrating the involvement in the disease by focusing on cutaneous leishmaniasis. Up to now, the role of many cytokines has been determined and the literature review showed that IL-35 is the latest known cytokine involved in leishmaniasis. This review revealed that the cytokines have pleiotropic effects, depending upon the cytokine environment, generated during the infection and the host genetic background or infecting Leishmania spp. Overall, advances in our knowledge of immune cells and their secreted cytokines, contributing to the protection or pathological process of leishmaniasis may help to reach new approaches for immunotherapy.

Real-time impact of COVID-19 pandemic on cutaneous leishmaniasis case finding and strategic planning, preventive interventions, control and epidemiology in a region with a high burden of cutaneous leishmaniasis and COVID-19: A cross-sectional descriptive study based on registry data in Ilam-Iran.

Background and Aims: Cutaneous leishmaniasis (CL) is a severe parasitic disease affecting people, mostly in underdeveloped nations. As a zoonotic infection yearly incidence of CL depends on several parameters such as demographic, epidemiological, and environmental factors as well as prevention and control measures. The sudden outbreak of pandemics such as SARS-Corona-Virus-2 pandemic, can probably affect the incidence or reporting of other diseases, especially infectious diseases, in various ways such as pressure on health systems, providing sanitary services and its components, lockdowns and changes in people's living habits. Aim: This study aimed to evaluate the COVID-19 impact on the incidence and other epidemiological aspects as well as control measures of CL in Ilam Province-Iran. Methods: Required data was extracted from the CL registration system in Ilam from 2014 to 2021 to demonstrate the trend of CL incidence before and after COVID-19 pandemic. Results: Based on our results, a declining pattern of CL incidence was observed, accompanied by the advent and intensification of the viral pandemic in Iran and Ilam province. Although, this decreasing pattern was not integral in all areas, and even increase in CL detection was emphasized in some regions. Conclusion: It may be inferred that the COVID-19 pandemic may disrupt treatment programs of CL cases, rodent nest destruction, and fighting vector insects.

In vitro antileishmanial activity of hydroalcoholic Thymbra spicata extract on Leishmania major promastigotes.

Cutaneous leishmaniosis is a major worldwide public health problem with annual incidence of 1.5 million cases across 98 countries. Treatment still relies on the use of chemical drugs with increasing resistance and side effects. The aim of this study was to investigate the anti-leishmanial effect of the hydroalcoholic Thymbra spicata extract on Leishmania major (L. major) promastigotes. In this study, 1×105 L. major promastigotes were cultured in 96-well plates and treated with different concentrations of hydroalcoholic T. spicata extract (12.5 to 400 µg/ml) then incubated at 25°C for 24, 48 and 72 hours. Lethal percentage of promastigotes in each well was determined. RPMI 1640 medium containing L. major promastigotes with glucantime or without any treatment were used as positive and negative controls respectively. The 50% lethal concentration (LC50) of T. spicata extract and glucantime was calculated by GraphPad Prism software. The results indicated a significant decrease in the number of promastigotes treated with T. spicata extract and glucantime in comparison with negative control (P<0.0001). LC50 values for T. spicata extract were 18.49, 8.58, and 1.64 µg/ml after 24, 48 and 72 hours, respectively. In addition, anti-leishmanial effect of T. spicata extract and glucantime were dependent on concentration (P<0.0001). Our study revealed T. spicata extract as an herbal product against L. major promastigotes. However, more investigations are needed to find its antileishmanial activity in vivo and clinical trial studies.

Global seroprevalence of Toxoplasma gondii in Camelidae: A systematic review and meta-analysis.

PURPOSE: The present study aimed to analyze data available of the seroprevalence of Toxoplasma gondii (T. gondii) among camelids around the world. METHODS: The search was performed using seven international databases including Scopus, PubMed, Google Scholar, ProQuest, ScienceDirect, Web of Science, and EMBASE up to 11 October 2018. Random effects model was used to determine the pooled seroprevalence of T. gondii infection with 95% confidence intervals (CI) and analyzed data from four continents. Subgroup and meta-regression analyses were also performed according to continent and gender. RESULTS: In total, 42 studies out of 3517 published articles involving 14,542 camels from 17 countries were included for the final analyses. The global pooled seroprevalence of T. gondii infection in the Camelidae family was 28.16% (95% CI 23.64-32.68%). Besides, the highest seroprevalence rate was in Europe (49.64%) followed by Africa (37.63%), America (21.76%), and Asia (17.58%). Moreover, the overall seroprevalence rates of T. gondii infection were 22% (95% CI 10-33%) and 15% (95% CI 9-22%) for the females and males, respectively. CONCLUSION: This meta-analysis showed a high seroprevalence of T. gondii infection in camelids as these animals play an important role in the transmission cycle of this zoonotic disease.

Comparative Assessment of Induced Immune Responses Following Intramuscular Immunization with Fusion and Cocktail of LeIF, LACK and TSA Genes Against Cutaneous Leishmaniasis in BALB/c Mice.

In the present study, we evaluated induced immune responses following DNA vaccine containing cocktail or fusion of LeIF, LACK and TSA genes or each gene alone. Mice were injected with 100 µg of each plasmid containing the gene of insert, plasmid DNA alone as the first control group or phosphate buffer saline as the second control group. Then, cellular and humoral responses, lesion size were measured for all groups. All vaccinated mice induced Th1 immune responses against Leishmania characterized by higher IFN-γ and IgG2a levels compared with control groups (p < 0.05). In addition, IFN-γ levels increased in groups immunized with fusion and cocktail vaccines in comparison with LACK (p < 0.001) and LeIF (p < 0.01) groups after challenge. In addition, fusion and cocktail groups produced higher IgG2a values than groups vaccinated with a gene alone (p < 0.05). Lesion progression delayed for all immunized groups compared with control groups from 5th week post-infection (p < 0.05). Mean lesion size decreased in immunized mice with fusion DNA than three groups vaccinated with one gene alone (p < 0.05). While, lesion size decreased significantly in cocktail recipient group than LeIF recipient group (p < 0.05). There was no difference in lesion size between fusion and cocktail groups. Overall, immunized mice with cocktail and fusion vaccines showed stronger Th1 response by production of higher IFN-γ and IgG2a and showed smaller mean lesion size. Therefore, use of multiple antigens can improve induced immune responses by DNA vaccination.

Expression of Plasmid Encoded GRA4 Gene of Toxoplasma gondii RH Strain in CHO Eukaryotic Cells.

BACKGROUND: Toxoplasmosis is a common infection all around the world. During pregnancy; it may lead to congenital disorders or abortion in human and animals. Severe damage of toxoplasmosis indicates to require effective vaccine. One of dense granules antigen is GRA4 that secrete from tachyzoite and bradyzoite. GRA4 genome is unique without intron and is one of the major immunogenic proteins from Toxoplasma gondii. METHODS: We confirmed the cloning of GRA4 gene into pcDNA3 by restriction enzyme and PCR of GRA4 gene with pcGRA4 plasmids as template. Then with using calcium-phosphate method we transfected the pcGRA4 into CHO (Chinesehamster ovary) cells. The yielded protein was separated by SDS-PAGE and moved by electroblotting to nitrocellulose paper. RESULTS: Result of SDS-PAGE analysis showed the appearance of band approximately 42 kDa which was absent in the negative control, that was able to identify toxoplasmosis antibody IgM+ serum in western blot analysis. CONCLUSION: pcGRA4 plasmid is able to synthesis of antigenic protein in CHO cells. The ability of pcGRA4 for induction of protective immune response against toxoplasmosis will be evaluated in mouse model.

Wound healing in cutaneous leishmaniasis: A double edged sword of IL-10 and TGF-ß.

Immune responses have a crucial role during the wound healing process in cutaneous leishmaniasis (CL). However, there are several paradoxes in immunity against CL. On the one hand, regulatory cytokines interleukin (IL)-10 and transforming growth factor beta (TGF-ß) increase susceptibility to CL through suppression of several proinflammatory cytokines that require for defense against CL. On the other hand, these cytokines play a pivotal role in the acceleration of wound healing process. This review discusses about the dual role of IL-10 and TGF-ß during the wound healing process and immunity against CL to offer a new insight about wound healing in CL.

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis.

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF-TSA fusion against cutaneous leishmaniasis pEGFP-N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3-12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN-γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF-TSA, respectively, than in PBS group at 12th week post infection. IFN/IL-4 and IgG2a/IgG1 ratios indicated that group receiving LeIF-TSA fusion had the highest IFN-γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN-γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.

Pro- and anti-inflammatory cytokines in cutaneous leishmaniasis: a review.

Cutaneous leishmaniasis (CL) is caused by different species of the genus Leishmania. Pro- and anti-inflammatory cytokines play different roles in resistance/susceptibility and the immunopathogenesis of Leishmania infection. The balance and dynamic changes in cytokines may control or predict clinical outcome. T helper 1 (Th1) inflammatory cytokines (especially interferon-γ, tumor necrosis factor-α and interleukin-12) are the crucial factors in the initiation of protective immunity against L. major infection, whereas T helper 2 cytokines including IL-5, IL-4, and IL-13 facilitate the persistence of parasites by downregulating the Th1 immune response. On the other hand, aggravation of inflammatory reactions leads to collateral tissue damage and formation of ulcer. For this reason, immunity system such as T regulatory cells produce regulatory cytokines such as transforming growth factor-ß and IL-10 to inhibit possible injures caused by increased inflammatory responses in infection site. In this article, we review the role of pro- and anti-inflammatory cytokines in the immunoprotection and immunopathology of CL.