Malaria pathogenesis is driven by intricate host–parasite interactions that determine immune balance and clinical outcome. The Plasmodium yoelii model particularly its lethal (17XL) and non-lethal (17XNL) strains provides a robust framework to investigate these dynamics. This review integrates recent findings demonstrating that 17XL infections trigger excessive pro-inflammatory cytokine release and immune exhaustion, while 17XNL infections sustain regulated Th1/Th2 responses enabling parasite control and survival. Emerging pathways involving MIF, TLR7 signaling, and immune checkpoints (PD-1, LAG-3) underscore the immunological divergence between strains. Evidence converges on a central concept: malaria severity reflects not parasite load but the timing and resolution of host immune responses. Future research using humanized models, single-cell profiling, and immunomodulatory interventions will deepen our understanding of immune regulation and guide novel therapeutic and vaccine strategies against malaria.

CD154 (CD40L) is of central importance in effector responses mediated by classically activated macrophages. However, there is limited information on the impact of CD154 on macrophage responses in type 2 contexts, characterized by IL-4-induced polarization and proliferation. CD154 restricts the polarization and proliferation of peritoneal cavity macrophages in response to exogenous IL-4. Here we address the impact of CD154 on peritoneal macrophages during infection of mice with the intestinal helminth Heligmosomoides polygyrus. This strictly enteric nematode causes recruitment of Th2 cells and macrophages to the peritoneal cavity alongside type 2 polarization and proliferation of recruited and resident macrophages. Nine days post-infection, there was an increase in the expression of cell-surface CD154 in CD4 + T cells together with increased IL-13 levels in the cavity, suggestive of local antigen presentation. Blocking CD154 enhanced the proliferation of resident but not of recently recruited macrophages. CD154 blocking additionally potentiated the expression of type 2 marker Ym1 ( Chil3) in resident and recruited macrophages. Unexpectedly, CD154 blocking caused increases in the numbers of recently recruited macrophages and appearance of cells with characteristics of both differentiating recruited macrophages (expression of folate receptor β and MHCII) and resident macrophages (high-level expression of F4/80 and CD102). Together, these observations suggest that CD154 promotes the acquisition of tissue residence by recruited macrophages. Thus, our results indicate that in a helminth infection CD154 restricts certain aspects of the polarization and proliferation of macrophages in response to type 2 cytokines while promoting the acquisition of resident phenotype by the recruited macrophages.

This study aimed to elucidate how osteopontin (OPN) affects the growth, invasion, and extrahepatic metastasis of Echinococcus multilocularis (Em) through the p38MAPK signaling pathway of host hepatocytes. C57BL/6J mice were randomly divided into the control group (n = 10), the LV-OPN-0423 group (n = 10), the anti-p38MAPK group (n = 10), and the anti-p38MAPK+LV-OPN-0423 group (n = 10). Em infection models in mice were set up. The mice were fed for 6 weeks under suitable conditions. The mice in the anti-p38MAPK group and the anti-p38MAPK+LV-OPN-0423 group were then given SB202190 (this is an inhibitor of p38MAPK) for 4 weeks, and the mice in each group were injected with corresponding lentivirus diluent once a week for 8 weeks. After the intervention was completed, the liver volume and weight were measured, and the liver was embedded in paraffin and sectioned. Sections were subjected to hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and immunohistochemical staining to observe the growth and invasion of Em, as well as the expression levels of OPN, p38MAPK, and p-p38MAPK of the host. SB202190 hindered Em’s growth, invasion, and migration. The level of OPN facilitated Em’s growth, invasion, and migration, which can be reversed by SB202190. The OPN level promoted the expression of p38MAPK and p-p38MAPK. These results suggested that OPN could regulate Em’s growth and metastasis through the P38MAPK signaling pathway in host hepatocytes, providing evidence that OPN and p38MAPK may be novel molecular targets for treating alveolar echinococcosis.

Human babesiosis is an emerging infectious disease caused by a blood-borne single-celled parasite belonging to the genus Babesia. Cases of human babesiosis are commonly reported in the United States, Western Europe, and Asia . In the United States, the two most common species are Babesia microti and Babesia duncani. Transmitted to humans through tick bites, the parasite infects the host’s red blood cells and induces flu-like symptoms, and has evolved mechanisms to manipulate the immune system, enabling its persistence. One key mechanism is the secretion of extracellular vesicles which carry bioactive molecules including proteins, lipids and genetic material that modulate pathogen-host interactions and disease development. The inhibition of the secretion of these vesicles may lead to disease control. One potential inhibitor of extracellular vesicle secretion is linoleic acid, a poly-unsaturated lipid that has demonstrated inhibitory properties in other parasites. To study the effects of development stage- dependent stimulus on Babesia duncani, we also examined the use of sorbitol, a sugar alcohol, to synchronize parasites. In this study, using a Babesia duncani in vitro continuous culture system and microscopy techniques, we showed sorbitol-induced synchronization of parasite development, and the inhibition of extracellular vesicle secretion.

not-yet-known not-yet-known not-yet-known unknown Introduction: Evidence from multiple data sources indicates that toxocariasis might play a role in the allergic asthma in children. This case-control study investigated the connection between Toxocara seropositivity and allergic asthma. It also sought to identify the conventional risk factors associated with both asthma and Toxocara infection. Methods: In this case-control study, 200 allergic asthma children, and 208 children with no history of allergic asthma were included as the healthy group. Sera samples were examined for specific anti-Toxocara IgG antibodies using a serological assay. Results: The overall prevalence of toxocariasis was 6.9% among children. The seroprevalence of toxocariasis in asthmatic children and healthy children was 8% and 5.8% respectively, with no significant difference (P-value= 0.373). In subgroup analyses based on sociodemographic, Toxocara infection seropositivity was significantly associated with two independent variables, including the father’s occupation (P-value = 0.017) and soil contact in asthmatic children (P-value = 0.033). Conclusions: Our results showed a higher prevalence of Toxocara infection in asthmatic children compared to healthy controls, but this difference was not statistically significant. To gain a clearer understanding and comparison of Toxocara infection rates between asthmatic and healthy children, additional comprehensive studies with larger sample sizes and diverse detection methods using different antigenic sources are required.

Trypanosome parasites of the genus Trypanosoma cause African animal trypanosomosis, a devastating livestock disease plaguing sub-Saharan Africa. Unlike many protozoan parasites, these extracellular blood-borne pathogens directly engage the host’s immune system. While the mouse model has provided valuable insights, a comprehensive understanding of the bovine immune response to trypanosomes remains elusive. Addressing immune response in cattle, the most relevant host species, and how it takes part in mitigating the negative impact of the disease could contribute to set up sustainable control strategies. This review summarizes the current knowledge of the immune response in cattle during trypanosomosis. Following a brief overview of infection processes and bovine trypanotolerance, we delved into the key immunological players: cellular and humoral immunity, cytokine regulation, and immune suppression. We discuss how these mechanisms contribute to tolerance or susceptibility to infection, highlighting critical gaps in knowledge that need further investigation.

Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is this larva is being protected by the acellular laminated layer (LL), made up of mucins and calcium inositol hexakisphosphate (Ins P 6). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite’s vicinity. Although foreign particles accumulating in tissues usually cause inflammation, the LL displays adaptations for minimising various host responses, and in vivo evidence of inflammation induced by LL particles is essentially lacking. In this work, we show that LL particles injected i.p. at a dose of 225 μg dry mass per mouse cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as disappearance of resident (large peritoneal) macrophages. The calcium Ins P 6 component was dispensable for these responses. Oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils but the carbohydrate-oxidized particles caused cell influx nonetheless. The control of local granulomatous inflammation is key for survival of this larva. Therefore, our results suggest that E. granulosus must deploy mechanisms to avoid excessive local build-up of LL particles (such as targeting particles to liver Kupffer cells; Infect Immun 91:e0003123) and/or to condition the recruited cells towards immune-regulatory phenotypes.

Abstract Ticks are notorious blood-sucking ectoparasites affecting both humans and animals, and serve as a unique vector of various deadly diseases. Here, we have shown the roles of the receptor for advanced glycation end-products (RAGE) during repeated infestations by the tick, Haemaphysalis longicornis using RAGE-/- mice. In primary infestation, a large blood pool developed which was flooded with numerous RBC, especially during the rapid feeding phase of the tick both in wild type (wt) and RAGE-/- mice. Very few inflammatory cells were detected around the zones of hemorrhage in the primary infestations. However, number of inflammatory cells gradually increased in the subsequent tick infestations and at the 3 rd infestations number of inflammatory cells reached to the highest level (350.3±16.8 cells/focus), and the site of attachment was totally occupied by the inflammatory cells in wild type (wt) mice whereas very few cells were detected at the ticks’ biting sites in RAGE-/- mice. RAGE was highly expressed in the 3 rd infestation in wt mice. In the 3 rd infestation, infiltration of innate lymphoid cells type 2 (ILC2s), expression of S100A8 and S100B significantly increased at the biting sites of ticks in wt, but not in RAGE -/- mice. Also, peripheral eosinophil counts significantly increased in wt but not in RAGE -/- mice. Taken together, our study revealed that RAGE-mediated inflammation and eosinophils played crucial roles in the tick induced inflammatory reactions.

Background: Leishmanization using non-pathogenic to human Leishmania spp. is considered a reliable approach to immunize subjects against Leishmania infection. Objectives: Here, we evaluated the long-term immune responses (14 weeks) after immunization with either live- or killed-Iranian Lizard Leishmania (ILL) mixed with chitin microparticles (CMPs) against L. major infection in BALB/c mice. Methods: In total, nine groups of mice were included in the study. To evaluate short-term immunity, mice were immunized with live-ILL and three weeks later were challenged with L. majorEGFP. To evaluate the long-term immunity, mice were immunized with either live- or killed-ILL, and 14 weeks after immunization were challenged with L. majorEGFP. A group of healthy mice who received no injection was also included in the study. Eight weeks after the challenge with L. majorEGFP all subjects were sacrificed and the parasite burden (quantitative real-time PCR), cytokines levels (IFN-γ, IL-4, and IL-10), Leishmania-specific antibody concentration, and total levels of IgG1 and IgG2a were measured. In addition, nitric oxide concentration, and arginase activity were evaluated. Results: In mice that were immunized using live-ILL+CMP, the induced proactive immune response lasted at least 14 weeks since, when they were challenged with L. major EGFP at the 14 th-week post-immunization, no open lesion was formed during 8 weeks follow-up, and the footpad swelling was significantly lower than controls. As well, they showed a significant reduction in the parasite burden in splenocytes, in comparison to the control groups including the group that received killed-ILL+CMP. The observed protection was associated with a higher IFN-γ and a lower IL-10 production by splenocytes. Additionally, the results demonstrated that arginase activity was decreased in the ILL+CpG group compared to other groups. Conclusion: The long-term response against L. major infection induced by Live-ILL+CMP was more competent than the response elicited by killed-ILL+CMP to protect mice against infection with L. major EGFP.

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 .

Background and objectives: A role of IL-10 is down-regulating T cell responses to schistosome antigens. Since SmATPDases can be correlated to modulation of the immune response, we evaluated the expression of enzymes in S. mansoni eggs. Patients/Methods: Fecal samples were collected from 40 infected individuals to detect coding regions of the SmATPDases. The cytokines was measured in supernatants of PBMC. The analysis was performed by the global median determination and set up high producers (HP) of cytokines. Results: Six individuals expressed SmATPDase1, six expressed SmATPDase2, and six expressed both enzymes. The group who expressed only SmATPDase1 showed a high frequency of IFN-γ, TNF, IL-4 HP, individuals who expressed only SmATPDase2 showed a high frequency of IFN-γ, IL-6, and IL-4 HP and individuals who expressed both enzymes showed a high frequency of IL-10 HP. In the group that showed expression both enzymes was observed lower indices the ratio between IFN-γ/IL-10. The positive correlation between infection intensity and IL-10 levels remained only in the positive SmATPDase group. The IL-10 is the only cytokine induced by the expression of both enzymes. Conclusions: The expression of both enzymes seems to be a factor that modulates the host immune response by inducing high IL-10 production.

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.