Malaria caused by Plasmodium parasites remains as a major global disease burden. While Plasmodium is developing within the infected red blood cells, they are protected from host innate immune response. However, when schizont ruptures releasing merozoites, many Plasmodium antigens are released, activating the host innate and adaptive immune system. This blood-stage infection is managed by the production of high-affinity antibodies by plasma cells, through germinal center (GC) reactions and, a quick low-affinity antibodies by extra follicular (EF) reactions within secondary lymphoid organs (SLOs) by conventional and non-conventional B cells. However, it is known that Plasmodium infection alters the formation of GCs and the antibody production. Currently, there is limited information about the relation between Plasmodium, conventional and non-conventional B cells. Here, using the Plasmodium berghei rodent malaria model, we studied the dynamic of conventional and non-conventional B cells during blood-stage malaria infection in the spleen and the peritoneal cavity. Eight-weeks-old male BALB/c mice were infected intraperitoneally with P. berghei ANKA strain, when 80% parasitemia was reached, the spleen was obtained, and the presence of conventional and non-conventional B cells were analyzed both, in spleen and peritoneal lavages by flow cytometry using specific antibodies. In the spleen of P. berghei infected mice, a significantly higher number and proportion of non-conventional B cells [B1 (B1a and B1b) and marginal zone B cells] were observed, while significantly lower percentages and number of conventional B cells (B-2) were observed in relation to uninfected mice. These results indicate that when Plasmodium alters the dynamics of GCs delaying the clearance of the parasite, the immune system conducts a compensatory response, inducing the activation and proliferation of non-conventional B cells to cope with Plasmodium infection. The understanding of the participation of B non-conventional cells populations during malaria infection would contribute to explain disease outcomes.

Background and Aim: Hydatidosis is a chronic zoonotic parasitic disease with global distribution, which affects the immune system. Inhibition of CD28 expression and elevation o inhibitory receptor like TIM3 induce T cells toward senescence differentiation, and causes immune responses to be adjusted negatively during the chronic infection. The purpose of the present study was to investigate expression of CD28 and TIM3 in CD8+ T cell population and IL-35 and IL-37 in serum of patients with hydatid cysts. Methods: The PBMCs of patients with hydatid cysts (before and after surgery) and healthy subjects (control) were separated. The expression of CD8, CD28, CD3, and TIM3 were examined with the flow cytometry method. The inflammatory cytokines were also examined with the ELISA method after the subjects’ blood serums were collected. Results: The results demonstrated a significant decreased in expression of TIM3 in the hydatidosis patients before surgery (P<0.05). CD8+CD28- cell population in the group of patients exhibited a significant decrease before surgery (P<0.05) in contrast to the control group. IL-35 in the two groups of patients, before and after surgery, exhibited a significant increase (P<0.05). Conclusion: The expression of T cells senescence markers decreased in patients with hydatid cysts and hydatidosis could partially inhibits the senescence T cells induction. Identification the senescence preventing mechanisms could reveal new therapeutic ways to prevent age-related diseases such as cancer.

backend=biber, style=alphabetic, sorting=ynt ]biblatex Introduction: Trypanosoma cruzi infection, which causes Chagas’ disease, induces an immune response in the host whose efficiency is important for the infection to persist or be eliminated. Alcohol consumption produces a great impact on the immune system, inducing alterations in the determination of T lymphocyte effector function, directing the profile of these cells to tolerance or inflammation. Our study aimed to evaluate, in C57BL/6 mice, the cytokine production in splenic leukocytes from T. cruzi infected and treated (EtOH) for 15 days and controls. Methods: Twenty-four mice were randomized into four groups, with 12 animals each: (1) Non-Infected Control (NI), (2) Control Infected (CI), (3) Experimental Non-Infected (EtOH -NI), and (4) Experimental Infected (EtOH -I). Results: Ethanol-pre-exposed infected mice exhibited elevated parasitemia during the patent period compared to controls. Adaptive immunity was characterized by increased IL-4, IL-10, and IFN-γ production by CD8+ T lymphocytes, while innate immunity showed reduced cytokine production, particularly in NK cells and macrophages. Ethanol amplified IL-10 and IFN-γ responses in macrophages yet suppressed TNF-α production in dendritic cells and macrophages during infection. Conclusion: These findings suggest ethanol modulates the immune response by enhancing adaptive immunity while impairing innate mechanisms, contributing to altered host-pathogen dynamics in T. cruzi infection.

To study on the proteome and to investigate the immune response mechanisms in P. skrjabini infection. Serum samples were randomly collected from patients with P. skrjabini infection and healthy individuals in Guizhou Province. ITRAQ (Isobaric Tags for Relative and Absolute Quantitation) assays were utilized for the analysis of protein catalogs in serum samples. Bioinformatics analysis on the differed proteins was performed. River crabs were sampled from the patients’ habitats, Paragonimus metacercariae were isolated for subsequent rat experimental infection. White blood cells and serum were collected at 42 days post-infection, changes in the expression of IL-4 were assessed. In result, a total of 50 proteins were identified. Typically, increased expression neutrophil defensin 3, protein S100-A9 (S100A9) and serum amyloid A-1 protein (SAA1) were found. S100A9 and SAA1 were involved in the main network but DEFA3 was not. The interaction networks were constituted with the core of Apolipoproteins family and the interactions with the fibrinogen and fibrinolytic system. Through subsequent experimental infections in rats, the expression of Th2 cytokines IL-4 remains unaltered. In conclusion, neutrophils may play a pivotal role in the elimination of parasites, whereas host Th2 cell immune response is suppressed in eliminating worms.

Co-evolutionary adaptation of hookworms with their mammalian hosts has selected for immunoregulatory excretory/secretory (E/S) products. However, it is not known whether, or if so, how host immunological status impacts the secreted profile of hematophagous adult worms. This study interrogated the impact of host Signal and transducer of activator of transcription 6 (STAT6) expression during experimental evolution of hookworms through sequential passage of the life-cycle in either STAT6 deficient or WT C57BL/6 mice. Proteomic analysis of E/S products by LC-MS showed increased abundance of 15 proteins, including myosin-3, related to muscle function, and aconitate hydratase, related to iron homeostasis. However, most E/S proteins (174 of 337 unique identities) were decreased, including those in the Ancylostoma-secreted protein (ASP) category, and metallopeptidases. Several identified proteins are established immune-modulators such as fatty acid-binding protein homolog, cystatin, and acetylcholinesterase. Enrichment analysis of InterPro functional categories showed down-regulation of Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP), Astacin-like metallopeptidase, Glycoside hydrolase, and Transthyretin-like protein groups in STAT6 KO adapted worms. Taken together, these data indicate that in an environment lacking Type 2 immunity, hookworms alter their secretome by reducing immune evasion proteins- and increasing locomotor- and feeding-associated proteins.

Aim: Natural transmission of Trypanosoma cruzi occurs when infected hematophagous deposit feces contaminated with metacyclic trypomastigotes on injured skin or mucosa. To study the inflammatory response at the inoculation site, dissemination of parasites, Th cell subtypes at the local lymph nodes and myocarditis mice were exposed to Triatoma dimidiata naturally contaminated with Trypanosoma cruzi. Methods and results: Mice were intradermal inoculated with T. dimidiata feces containing metacyclic trypomastigotes or were previously immunized with feces without metacyclic trypomastigotes and analyzed from 15 minutes to 3 months after inoculation. Parasites remained at the inoculation site until 20 days after inoculation but disappeared early in pre-immunized mice that presented with edema and collagen fragmentation as early as 15 minutes after being challenged with metacyclic trypomastigotes. The Th2 subpopulation dominated in the first week in mice infected with feces containing metacyclic trypomastigotes, whereas Th1 and Th17 populations dominated in the challenged mice population. Similarly in heart tissue, intense myocarditis and remodeling, with faster clearance of amastigotes was observed in mice previously immunized with Triatoma dimidiata feces. Furthermore, immune cell-types, Th1 and Th17, predominated after 20 days post-infection in all experimental groups. Conclusions: Previous exposure with Triatoma dimidiata feces prior to infection with metacyclic trypomastigotes favors parasitic dissemination and early induction of Th1 and Th17 subpopulations with lower parasitism in heart tissue but does not ameliorate inflammation and tissue damage which is accompanied with Th1/Th17 and Treg profile.

Introduction: The T-cell subset (CD4+Tregs) play a significant role in immunoregulation, by active suppression of the immune system, through cell-to-cell contact and the secretion of IL10. The frequencies of these cell subpopulations were investigated in the mother. Methods: The study recruited 61 mothers out of this number, 31 mothers with plasmodium parasitized placentas and 30 mothers without plasmodium infection. Placental malaria positivity was determined by PCR and microscopy. Peripheral mononuclear cells (PBMCs) were isolated from peripheral blood, cultured in the presence of VAR2CSA antigen, and stained with antibodies (CD3, CD4, CD25, and IL-10), before cytometry analysis. Results: The CD4+CD25+ T cell frequencies were significantly higher in all the participants (p<0.0001), and comparable across gravida. These cell populations were similar when compared between primigravid and secumgravida mothers (p=0.77), and between multigravida and secumgravida mothers (p=0.84). Primigravid mothers with placental malaria had significantly higher frequencies of CD4+CD25+ T cell population (p=0.04). The frequencies of CD4+IL10 were significantly high in both primigravid and multigravid mothers who were placental malaria positive (p=0.03) and (p=0.04) respectively. Conclusion: Induced Tregs (CD4+IL10) cells could play a role in placental malaria susceptibility due to an increase in their populations in mothers with plasmodium-infected placentas.