The protozoan parasite Toxoplasma gondii infects approximately 2.5 billion people worldwide. Infection induces a rapid dissemination of parasites throughout the body followed by the formation of lifelong cysts within neurons of the host brain. Both stages require a dynamic immune response comprised of both innate and adaptive cells. Neutrophils are a primary responding cell to acute infection and have been observed in the brain during murine chronic infection. Previous studies investigating human neutrophils found that invasion by Toxoplasma tachyzoites inhibits apoptosis of neutrophils, prolonging their survival under inflammatory conditions. Here, we demonstrate the differentiation of two distinct subsets following exposure of human neutrophil-like-cells (HNLC) to Toxoplasma cysts. In vitro stimulation and imaging studies show cyst-specific induction of cytokines and cyst clearance by HNLCs. Further testing demonstrates that aged HNLCs perform less phagocytosis of cysts compared to non-aged HNLCs. In conclusion, this study identifies a novel response of HNLCs to Toxoplasma cysts and may indicate a role for neutrophils in the clearance of cysts during human infection with Toxoplasma.

Chagas disease is caused by the Trypanosoma cruzi parasite and is transmitted by infected triatomine bugs. This infection affects approximately 8 million people in the Americas, and due to globalization and displacement, it is becoming increasingly common to find infected patients worldwide. Diagnosis of the disease in its acute form is relatively simple, as the parasite can be detected in peripheral blood smears, and symptoms are visible. However, in its chronic condition, the parasite is almost undetectable, and indirect tests are necessary to determine the presence of antibodies in infected patients. It is important to note that a single test is not enough to confirm the disease, as a second serological test should confirm the diagnosis. If the results are contradictory, a third test should be performed to solve the problem. Unfortunately, laboratories may not have access to all necessary tests in many rural areas where the disease is more frequent. Rapid tests to diagnose this disease present problems, such as significant variations in sensitivity and specificity in different countries. Therefore, searching for new biomarkers that allow for optimal correlation is essential. In this work, we have searched scientific literature from the last years for mentions of novel biomarkers for diagnosis, treatment follow-up, and prediction of cardiac complications in Chagas disease in its chronic phase.

Alteration in the physiological state of the endoplasmic reticulum (ER) leads to the specific response known as unfolded protein response (UPR) or ER stress response. The UPR is driven by three sensor proteins, namely: Inositol Requiring Enzyme 1 (IRE1), Protein Kinase RNA like ER kinase (PERK), and Activating Transcription Factor 6 (ATF6) to restore ER homeostasis. Pathogenic infection can initiate UPR activation; some pathogens can subvert the UPR to promote their survival and replication. Many intracellular pathogens, including Leishmania, can interact and hijack ER for their survival and replication, triggering ER stress and subsequently ER stress response. This review aims to provide a comprehensive overview of the ER stress response in infections with the Leishmania species .

Goat warble fly infestation (GWFI) is an economically important myiasis caused by larvae of Przhevalskiana silenus (Diptera, Oestridae), prevalent in countries of the Mediterranean Basin and Indian subcontinent. GWFI is characterized by the presence of subcutaneous warbles at the lumbar and sacral region of dorsum in the infested animal. The early larval instars (L1 and L2) remain inaccessible to physical detection due to their small size and subcutaneous presence thus causing prolonged economic loss to animal productivity. The early diagnostic intervention is needed during the disease monitoring and prophylactic management for effective control of the disease. The present study has developed an in-house dot-ELISA for the serodiagnosis of GWFI based on recombinant Hypodermin C (rHyC) antigen of Przhevalskiana silenus, expressed in E. coli. The purified protein was used for optimizing dot-ELISA in a checkerboard titration using goat warble fly infested serum as known positive. The optimized conditions require 188 ng of protein/dot, 1:800 dilution of serum sample, 1:4000 dilution of anti-goat IgG conjugate and 5% skim milk powder in phosphate buffer saline as blocking buffer. The assay was found to have a diagnostic sensitivity and specificity of 97.3% and 95.8%, respectively. The inter-rater reliability of dot ELISA with rHyC indirect ELISA was found to be almost perfect with a Cohen’s kappa index of 0.973. Further testing at ambient temperature (18 oC) and shorter incubation steps (30 min) supported suitability of the assay for field diagnosis of GWFI. The rHyC protein based Dot-ELISA was evaluated using random field serum samples suspected for GWFI. The present study provides the first report of a sensitive and specific dot-ELISA for early diagnosis of GWFI which is rapid and cost effective. The test may provide an effective tool for sustainable control of GWFI.

Intestinal helminth infection promotes a Type 2 inflammatory response in resistant C57BL/6 mice that is essential for worm clearance. The study of inbred mouse strains has revealed factors that are critical for parasite resistance and delineated the role of Type 1 versus Type 2 immune responses in worm clearance. In C57BL/6 mice, basophils are key innate immune cells that promote Type 2 inflammation and are programmed via the Notch signaling pathway during infection with the helminth Trichuris muris. However, how the host genetic background influences basophil responses and basophil expression of Notch receptors remains unclear. Here we use genetically susceptible inbred AKR/J mice that have a Type 1-skewed immune response during T. muris infection to investigate basophil responses in a susceptible host. Basophil population expansion occurred in AKR/J mice even in the absence of fulminant Type 2 inflammation during T. muris infection. However, basophils in AKR/J mice did not robustly upregulate expression of the Notch2 receptor in response to infection as in C57BL/6 mice. Blockade of the Type 1 cytokine IFN-γ in infected AKR/J mice was not sufficient to elicit infection-induced basophil expression of the Notch2 receptor. These data suggest that the host genetic background, outside of the Type 1 skew, is important in regulating basophil responses during T. muris infection in susceptible AKR/J mice.

Background Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied, however immune cells in patients with different stages of Schistosomiasis Japonica are not well analyzed. Here we performed a preliminary study to explore characteristics of peripheral lymphocyte subsets in patients with different stages of Schistosomiasis Japonica. Methods 135 patients with S. japonicum infection and 25 healthy volunteers were included in this study, including 84 patients with chronic S. japonicum infection and 51 patients with advanced S. japonicum infection. Flow cytometry analysis was performed to evaluate peripheral lymphocytes including T cells, B cells and NK cells. Blood routine and liver function test data were analyzed. Ultrasound examination was used to access liver fibrosis according to the World Health Organization standard about ultrasound in schistosomiasis. Results Demographic data analysis suggested there was no difference in age and gender in patients with S. japonicum infection and health control group. Liver function tests showed that patients with advanced schistosomiasis had a higher incidence of liver function abnormality and blood lipid than those with chronic schistosomiasis. Blood routine results reflected that hemoglobin, red blood cells, platelets, as well as lymphocytes in the advanced group were significantly less than that in the chronic group. Furthermore, flow cytometry analysis indicated that the percentage of CD4 +T cells was lower in the advanced group, but the percentage of CD19 +B cells was higher in the advanced group. In addition, the number of CD3 +T cells, CD3 +CD4 +T cells, CD3 +CD8 +T cells, and NK cells was less in the advanced group when compared with those in the chronic group. In addition, there was a correlation between the decrease in CD4 + T cells and more severe fibrosis on ultrasound images. Conclusion Our results indicated that the immune state in the peripheral is different in different stages of S. japonicum infection. Lymphocyte subset analysis have potential to facilitate differential diagnosis of different stages of schistosomiasis japonica and even to be a prognostic factor.

During inflammation hematopoietic stem cells (HSCs) in the bone marrow (BM) and periphery rapidly expand and preferentially differentiate into myeloid cells that mediate innate immune responses. HSCs can be directed into quiescence or differentiation by sensing alterations to the hematopoietic niche, including cytokines, chemokines, and pathogen-derived products. Most studies attempting to identify the mechanisms of hematopoiesis have focused on bacterial and viral infections. From intracellular protozoan infections to large multicellular worms, parasites are a global health burden and represent major immunological challenges that remain poorly defined in the context of hematopoiesis. Immune responses to parasites vary drastically, and parasites have developed sophisticated immunomodulatory mechanisms that allow development of chronic infections. Recent advances in imaging, genomic sequencing and mouse models have shed new light on how parasites induce unique forms of emergency hematopoiesis. In addition, parasites can modify the hematopoiesis in the BM and periphery to improve their survival in the host. Parasites can also induce long-lasting modifications to HSCs, altering future immune responses to infection, inflammation or transplantation, a term sometimes referred to as central trained immunity. In this review, we highlight the current understanding of parasite-induced hematopoiesis and how parasites target this process to promote chronic infections.