José Rodrigues Do Carmo Neto

Rotavirus (RV) is one of the main etiologic agents associated with diarrheal diseases (DDs), being responsible for approximately 200 thousand deaths annually. Currently, there are still many aspects regarding the virus biology, cell cycle, and pathophysiology of RV that need further elucidation. Therefore, the present work aimed to investigate whether the triggering receptor expressed on myeloid cells 1 (TREM-1) might be associated with RV infection. This immune receptor has been observed as an amplifier of inflammatory responses in different infectious and non-infectious diseases, including inflammatory bowel disease and celiac disease. Initially, we searched for public transcriptomic data regarding RV infection and the expression of TREM-1 and its associated genes, which were significantly upregulated in infected mice and children. Then, we infected monocytes with the virus, with or without a TREM-1 inhibitor. The inhibition of the receptor’s activity resulted in a significant decrease in IL-1β production. We also observed a reduction in cytopathic effects when MA104 cells were treated with TREM-1 inhibitors and then infected with simian RV. To further elucidate the interactions between the virus and TREM-1, in silico tools were used to simulate interactions between the receptor and RV proteins. These simulations suggested the occurrence of interactions between TREM-1 and VP5*, a protein involved in viral attachment to target cells, and also between the receptor and NSP4, a viral enterotoxin with immunostimulant properties. Hence, our results indicate that TREM-1 is involved in RV infection, both as a mediator of inflammatory responses and as a player in the host–virus relationship.

Chagas disease (CD), caused by Trypanosoma cruzi, leads to cardiomyopathy in approximately 20–30% of infected individuals. Interleukin-11 (IL-11) has been implicated in cardiac fibrosis, although its immunological role in this context remains unclear. This study investigated the temporal dynamics of IL-11 and its receptor, IL-11Rα, expression in the hearts of C57BL/6 mice infected with 1,000 trypomastigote forms of the Y or Colombian strains of T. cruzi. Mice were euthanized at 5, 15, 30, 60, and 120 days post-infection (dpi). Survival, parasitemia, and body and heart weights were monitored. Cardiac tissue was analyzed for parasite nests, myocarditis, collagen deposition, and expression of the IL-11 receptor alpha (IL-11Rα). Cytokine profiles were evaluated by ELISA and Cytometric Bead Array. Histopathological analysis revealed more intense myocarditis, parasite load, and collagen deposition in mice infected with the Colombian strain. Both strains induced IFN-γ, TNF-α, and IL-6 in cardiac tissue; however, IL-10, IL-4, and IL-17 were detected only in the Y strain, indicating a more balanced immune response. Despite the absence of significant IL-11 upregulation in either infection, IL-11Rα expression was progressively increased over time and positively correlated with collagen deposition. These findings suggest that IL-11Rα may play a role in cardiac remodeling and fibrosis independently of IL-11 upregulation. The results reinforce the importance of T. cruzi strain variability in disease outcome and highlight the IL-11/IL-11Rα axis as a potential target for further investigation in Chagas cardiomyopathy. Graphical Abstract The kinetics of IL-11 and IL-11Rα expression in the heart during experimental Trypanosoma cruzi infection reveal striking differences between the Y and Colombian strains over time (5, 15, 30, 60, and 120 days post-infection). The shaded areas in green and orange represent IL-11Rα expression and IL-11 production, respectively. In the Y strain, IL-11 production is detectable throughout the infection, peaking around 30 days. In contrast, the Colombian strain exhibits lower IL-11 expression. IL-11Rα expression is upregulated in both strains: starting at 15 dpi in the Y strain and at 60 dpi in the Colombian strain, remaining elevated until 120 dpi. The colored lines indicate the kinetics of other parameters: Pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6): red; Regulatory/Th2/Th17 cytokines (IL-10, IL-4, IL-17): green; Cardiac parasitism (T. cruzi nests): purple; Inflammatory infiltrate: black; Collagen deposition: brown. The distinct peaks observed between groups reflect the specific immunopathological characteristics of each strain in terms of inflammation, immune response, and cardiac damage. This graphic scheme provides an integrated summary of the dynamics between the analyzed parameters throughout the course of infection.

The development of leishmaniasis depends on the ability of Leishmania to invade and survive within macrophages. Macrophages can either promote parasite elimination or support its survival, depending on whether they are classically (M1) or alternatively (M2) activated. Mice chronically infected with Taenia crassiceps cysticerci (TC) develop a predominantly Th2 immune response, which leads to an increased number of M2 macrophages. In this study, we assessed the susceptibility of BALB/c mice previously infected with TC to Leishmania (V.) braziliensis or Leishmania (L.) major. Mice were first inoculated intraperitoneally with TC and after eight weeks infected either L. (V.) braziliensis or L. (L.) major in the paw. We evaluated footpad swelling and parasite load in different organs. We also assessed parasite load in vitro at 3 h, 3, 6, and 9 days; nitric oxide (NO) production, and arginase activity. Macrophages obtained from TC-infected mice (TcMΦ) were more susceptible to L. (V.) braziliensis infection, maintaining a stable parasite load without significant proliferation, while the parasite was killed in thioglycolate-elicited macrophages (TgMΦ). In contrast, L. (L.) major proliferated intensely in TcMΦ, leading to a higher parasite load compared to TgMΦ. In vivo, infection with L. (V.) braziliensis in TC-coinfected mice did not alter the parasite load compared to the group without cysticerci. However, mice infected with L. (L.) major exhibited greater swelling and higher parasite burdens. These findings suggest that infection with TC modulates the immune response of mice but is unable to render resistant mice susceptible to L. (V.) braziliensis. Graphical Abstract

Background/Objectives: For the development of new treatments, the acute phase of Chagas disease (CD) in experimental models acts as a filter to screen out potentially effective interventions. Therefore, the aim of this study was to evaluate ZnO nanocrystals and Ag-ZnO/AgO nanocomposites containing different proportions of silver (ZnO:5Ag, ZnO:9Ag and ZnO:11Ag) in an experimental model of the acute phase of CD. Methods: C57Bl/6 mice were infected with 1000 forms of the Colombian strain of T. cruzi. The treatment was carried out by gavage with 5 mg/kg/d for 7 consecutive days from the first detection of parasitemia. Weight, parasitemia and survival were assessed during treatment and up to the day of euthanasia. After euthanasia, the cardiac and intestinal parasitism, inflammatory infiltrate, collagen deposition and cytokine dosages were analyzed. Results: It was observed that the nanocomposites ZnO:9Ag and ZnO:11Ag were the most effective in reducing parasitemia and increasing the survival of the infected animals. However, pure ZnO induced the maintenance of parasitemia and reduced their survival. The ZnO:9Ag and ZnO:11Ag nanocomposites were able to reduce the number of cardiac amastigote nests. In addition, they were responsible for reducing TNF-α and IL-6 in situ. ZnO:9Ag and ZnO:11Ag induced a reduction in the intestinal inflammatory infiltrate and neuronal protection in the myenteric plexus, as well as reducing TNF-α in situ. Conclusions: Based on these results, it is suggested that there is an ideal concentration in terms of the proportion of Ag/AgO and ZnO in nanocomposites for use against CD. Thus, ZnO:9Ag or ZnO:11Ag nanomaterials are potential candidates for the development of new biotechnological products for the therapy of CD.

Zinc oxide nanoparticles (ZnO NPs) are metal oxide nanomaterials, which are important for several applications: antibacterial, anthelmintic, antiprotozoal and antitumoral, among others. These applications are mainly related to the ability to spontaneously produce and induce the production of reactive oxygen species that are important components for the destruction of pathogens and tumor cells. While trying to potentiate ZnO NPs, studies have associated these NPs with silver oxide (AgO) or silver (Ag) NPs. It has already been reported that this combination (Ag-ZnO/AgO NPs) is able to enhance the microbicidal potential. Although possessing much potential for several purposes, it is important to evaluate whether this association also poses the risk of toxicity to cells and experimental models. Therefore, this work aimed to evaluate the toxicity of various Ag-ZnO/AgO NP nanocomposites, in vitro and in vivo. Accordingly, ZnO nanocrystals and nanocomposites with various concentrations of AgO (ZnO:5Ag, ZnO:9Ag or ZnO:11Ag) were used in different cytotoxicity models: Galleria mellonella (G. mellonella), cell lines (VERO and RAW 264.7) and C57BL/6 mice. In the G. mellonella model, four concentrations were used in a single dose, with subsequent evaluation of mortality. In the case of cells, serial concentrations starting at 125 µg/mL were used, with subsequent cytotoxicity assessment. Based on the safe doses obtained in G. mellonella and cell models, the best doses were used in mice, with subsequent evaluations of weight, biochemistry as also renal and liver histopathology. It was observed that the toxicity, although low, of the nanocomposites was dependent upon the concentration of AgO used in association with ZnO NPs, both in vitro and in vivo.

Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.

Pemphigus, an autoimmune intraepidermal bullous disease group with roughly eight distinct forms, includes pemphigus vulgaris (PV) and pemphigus foliaceus (PF) as its predominant global forms. Despite the increased utilization of global health records and reporting systems, epidemiological data remain limited and poorly categorized. Therefore, this study aimed to conduct a review to track, identify, and characterize cases of PV and PF published and categorized worldwide. A research question was formulated; studies were selected based on the inclusion criteria; and data from these publications were systematically collected, summarized, and presented using narrative descriptions. The search strategy yielded 3,212 articles, of which 95 underwent critical analysis and data extraction. Studies from 52 countries contributed to the dataset, covering various pemphigus variants. Notably, only two countries, Iran (18.87%) and South Korea (11.43%), accounted for approximately a third of the reported PV cases, while Brazil contributed 40.25% of the foliaceus variants cases documented in the literature. These findings offer valuable insights into the global distribution of pemphigus and inform future research and healthcare efforts.