We studied the cellular immune response in a patient infected since 10 months (along with other 51 people) during a trichinellosis outbreak caused by Trichinella spp.

The role of the innate immune system in polycystic liver disease (PLD) has been underexplored despite its potential importance in disease progression. This study explores the innate immune response in PLD patients by analyzing cytokine production of peripheral blood mononuclear cells (PBMCs) in response to various pathogens compared to healthy controls.

The Cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes [1] signaling pathway has emerged as a pivotal immune response mechanism, activating immune defenses upon detection of both exogenous and endogenous DNA within cells. Its activation is intricately linked to various diseases and inflammatory processes, spanning autoimmune disorders, infectious ailments, and malignancies. Among pancreatic diseases, encompassing acute pancreatitis, chronic pancreatitis, and pancreatic cancer, current clinical treatment efficacy remains suboptimal. Here, we elucidate the molecular intricacies of the cGAS-STING signaling pathway and delineate its therapeutic potential in acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Additionally, we offer an overview of recent advancements in STING agonists and antagonists, assessing their therapeutic potential in pancreatic-related disorders. In summary, by exploring the multifaceted roles of the cGAS-STING signaling pathway and its implications in pancreatic diseases, we aim to shed light on potential avenues for therapeutic intervention and management in these challenging clinical contexts.

Cytokines are highly conserved between mammals and insects. The present study examines the multiple effects of interferon-gamma (IFN-γ) application on the immunological defence mechanisms of Galleria mellonella larvae, invertebrates which are gaining popularity as a replacement for mammalian research models in immunological studies. G. mellonella hemolymph is known to contain an IFN-γ homolog that shares 33 % similarity with its mammalian analogue, and its level in insect hemocytes increases during exposition to entomopathogenic fungus Conidiobolus coronatus. The present research examines the impact of IFN-γ on larval development, the effectiveness of fungal infection, and the morphology and physiology of wax moth immunocompetent cells. Treatment with IFN-γ enhanced wound healing, chemotaxis activity and hemocyte impedance, while reducing hemocyte phagocytosis and oxidative stress in cultured immunocompetent cells; it also appears to increase the levels of Jak-2- and NF-κB-like molecules in hemocytes. Our findings suggest that IFN-γ demonstrated considerable similarity between mammals and humans, thus further demonstrating the evolutionary conservatism of cytokines.

Some pro-inflammatory and anti-inflammatory cytokines were significantly elevated in patients with candidemia patients, but no studies have included these cytokines in the analysis of risk factors for mortality of candidemia. This study aims to analyze the risk factors of short-term mortality of candidemia and the predictive value of serum cytokines.

Sepsis is an uncontrolled inflammatory response to infection and is closely associated with the occurrence of acute respiratory distress syndrome (ARDS). Low tidal volume lung ventilation and permissive hypercapnia is a recognized therapy for ARDS. However, whether permissive hypercapnia aggravates sepsis-associated encephalopathy (SAE) remains unclear. The present study investigated whether hypercapnia contributed to the development of SAE through the purinergic 2X7 receptor (P2X7R) by activating the Nod-like receptor protein 3 (NLRP3) inflammasome in sepsis.

Immunological aspects of B. mallei infection were rarely studied in natural cases of equines. The present study was conducted to determine IgG, IgM, IgA and IgG (T) titre against recombinant Hcp1, TssA and TssB proteins and PilA-Hcp1-TssN-BipD and BpaB-BpaC- BMAA0553 chimeras and cytokine responses in glanders affected equine serum.

Elevated inflammation contributes to growth faltering in children. Vitamin D (vitD) suppresses pro-inflammatory and enhances anti-inflammatory molecule production, thus vitamin D deficiency (VDD) has been associated with heightened inflammation. In undernourished children, VDD and inflammation co-exist, however, little is known about their interaction.

Host-tissue preference is a critical aspect of parasitic infections and is directly correlated with species diversity. Even the same species, Leishmania donovani, infects the host's bone marrow, spleen, and liver differentially. The tissue-specific persistence of Leishmania results from host-pathogen immune conflicts and arguments. The protective pro-host or destructive pro-parasitic role of TLRs during L. donovani infection has been well established, but what entirely missing is the influence of TLRs on tissue-specific parasite persistence. We observed that the parasites induced differential expression of TLR1/2 in the bone marrow but not in the spleen. Interestingly, the rate of Leishmania infection was found to be positively correlated with TLR1/2-mediated upregulation of myelopoietic cytokines, M-CSF, GM-CSF, IL-6, and IL-3, leading to the expansion of Ly6CCCR2 monocytes, however, negatively correlated with the expression of the disease hallmark cytokines, TNF-α, TGF-β, and IL-10, along the course of infection in the bone marrow. Leishmania induced the activation of bone marrow-specific TLR1/2 to promote Ly6CCCR2 monocytes for its safe shelter vis-à-vis infection establishment. Consequently, the established infection initiated the release of TNF-α, TGF-β, and IL-10 in the bone marrow. Post-infection time-kinetic study affirmed that TGF-β had a significant negative influence on the expression of TLR1/2 heterodimer in the bone marrow niche. To the best of our knowledge, this is the first report to show that the inverse correlation of TLR1/2 - TGF-β can be instrumental in tissue-specific parasite persistence during Leishmania infection.

Kawasaki disease (KD) is a pediatric vasculitis that has a predilection for coronary artery involvement. Activated macrophages play an important role in the destruction of the coronary arteries in KD. Although intravenous immunoglobulin (IVIG) is standard therapy, corticosteroids are sometimes given to patients at a higher risk of IVIG non-responsiveness. In this study, we examined the effect of IVIG and corticosteroids in U937 derived M1 and M2 a macrophages.

Prior observational research has shown relationships between immune cells, inflammatory proteins, and autoimmune liver diseases (AILD), but their causal associations remain controversial. Therefore, we aimed to clarify the causal association between them.

This study investigates the immunopathological responses to Chlamydia trachomatis (Ct) heat shock protein (Ct-Hsp) and their association with infertility. The objective was to explore the prevalence of anti-Ct antibodies and the gyneco-epidemiological risk factors for infertility among women attending a fertility clinic in Zaria, Nigeria, and to analyze the host immune cytokine or Ct-antigen levels in Ct-positive samples for correlation. From December 2022 to January 2024, 215 women (109 infertile and 106 fertile) from Ahmadu Bello University Teaching Hospital participated in this study. Endocervical specimens were tested for Ct-specific IgM and IgG antibodies to identify current and past infections. Additionally, antibodies to Ct-Hsp60, and cytokine levels of IFN-γ and IL-10, were measured using ELISA kits. The overall prevalence of Ct infection was 9.3 %. Past infection, indicated by IgG, was 40 %, while current infection, indicated by IgM, was 25 %. The remaining 35 % of Ct infection were detected by both immunological assay. Among infertile women, primary and secondary infertility prevalence was 41 % and 59 %, respectively. Serum IL-10 levels were significantly higher in Ct-positive infertile women compared to fertile controls. Serum IFN-γ levels were higher in Ct-negative fertile and infertile women than in Ct-positive cases. Serum Ct-Hsp60 levels were significantly higher in Ct-positive fertile women compared to infertile cases. The Th1/Th2 cell ratio was lower in both fertile and infertile women, regardless of Ct status, but fertile controls had a higher Th1/Th2 ratio compared to Ct-positive infertile women. Logistic regression identified significant infertility risk factors: vaginal discharge, age, second marriage, increasing years of childless marriage, and being over 35 years. Protective factors included anti-Ct IgM antibodies, teaching, lower education, and more children. Higher secondary infertility prevalence was linked to family planning history and reactivity to Ct-Hsp60. Ct-positive cases were associated with tubal factor and pelvic inflammatory disease infertility. This study highlights a low overall prevalence of Ct infection but a higher prevalence in women with tubal factor infertility, emphasizing the need for further research on cytokine responses in Ct-associated infertility.

Omalizumab, an anti-IgE biological agent, is commonly prescribed as a second-line therapy for Chronic Spontaneous Urticaria (CSU). However, there is a lack of biomarkers to predict which CSU patients will respond favorably to omalizumab.

The epidermal growth factor receptor (EGFR) signaling pathway is crucial for skin barrier integrity and immune response. This study explores the impact of EGFR inhibitors, osimertinib and afatinib, on keratinocyte function, focusing on keratin (KRT1, KRT17) and tight junction protein (CLDN1, CLDN2, CLDN4) expression in HaCaT cells. Osimertinib significantly increased the mRNA and protein levels of keratins and inflammatory markers, IL-6 and TNF-α, via activation of the EGFR-STAT3 signaling pathway. Co-treatment with recombinant human EGF reversed these changes, suggesting the pathway's modulatory role. These findings underscore the potential therapeutic applications of targeting the EGFR-STAT3 axis in skin barrier dysfunction and inflammatory skin disorders.

To investigate anti-Mycobacterium tuberculosis (Mtb) influences exerted by natural killer cell-derived exosomes (NK-exo) on mice and to elucidate underlying immunologic mechanisms.

Visceral Leishmaniasis (VL) is an endemic disease in Latin America, and the clinical outcome worsens when a patient has HIV co-infection. In these patients, the immune response is complex and cytokines profile variable. We evaluate Th1/Th2/Th17 cytokine profile in VL/HIV patients from Brazilian high endemic area. In this cross-sectional study, the serological cytokines production was compared with clinical and epidemiological traits of the VL/HIV, VL and HIV patients. VL/HIV patients are predominantly male (89.2 %) with relapses in 35.5 % of the cases. There is higher serum levels of IL-6 (p = 0.006) and IL-10 (p < 0.001) in VL/HIV patients. Furthermore, there is a moderate or strong positive correlation in the serum levels of IL-6 and TNF-α (Rho = 0.635, p < 0.001), IL-10 and IFN-γ (Rho = 0.523, p < 0.001), IL-6 and IL-10 (Rho = 0.506, p < 0.001), IL-2 and IL-4 (Rho = 0.506, p < 0.001). Then, VL/HIV patients who died during VL treatment (p = 0.033), patients with oedema (p = 0.011), and patients with jaundice (p = 0.019) had statistically high levels of IL-6. In conclusion, VL/HIV patients have production or reduction of specific cytokines, highlights IL-6 and IL-10.

Chronic pain typically lasts or recurs for more than three months and is an unpleasant sensory and emotional experience, including neuropathic pain, long-term tissue damage, tumors, and viral or bacterial infections.The unpleasantness associated with pain affects the basic life of patients and has become a truly global problem. Macrophages, a powerful immune effector cell whose functional plasticity leads to polarization into different subtypes and opposite effects in different environments, are also indispensable in the development of pain.In recent years, there has been an increasing number of studies on the effects of macrophages on pain, and there are multiple pathways that regulate macrophage polarization, including lipopolysaccharide induction and IL-4/IL-13 stimulation.In addition, pathways involving macrophages and macrophage polarization have been found to have an exacerbating or mitigating role in the progression of chronic pain, with M1 macrophages generally exacerbating pain progression and M2 macrophages mitigating pain progression.Therefore, modulating macrophage polarization holds great promise as an intervention in chronic pain. In this paper, we synthesize multiple macrophage pathways as well as mechanisms affecting their pain processes in the context of different types of chronic pain, providing new avenues for chronic pain relief.

It remains difficult to evaluate the risk factors for concomitant carotid artery as well as coronary artery diseases in elderly patients. The aim of this research was to determine the TNF-α/IL-1β/IL-1α/IL-12 axes-TLR1/TLR3/TLR5/MYD88 immune signaling pathway interactions in coexistent carotid artery occlusion and coronary artery occlusion in elderly patients.

CD40-CD40-ligand (CD40L) interaction plays crucial immunoregulatory roles, as CD40 signals through different signaling intermediates to convert the messages from CD40L to effector functions. Being a TNFα receptor family member, CD40 binds TNFα receptor-associated factors, assembles signalosome complexes and decrypts the messages from CD40L through different signaling modules to result in residue-specific effector functions. The evidence for such a residue-specific message encryption first came from the CD40L mutations resulting in X-linked hyper-IgM syndrome, as the extent of effects varied with the residue mutated. The structural studies on the CD40-CD40L interaction implied differential involvement of the interacting residues on CD40L in influencing the effector functions. Three lines of evidence indicate the previously implied residue-specific message encryption in CD40L: screening of a dodecameric peptide library for CD40 binders identified two peptides with different sequences resulting in counteractive effector functions in macrophages; a series of CD40L mutants identified that the mutations in these residues selectively affected CD40 signaling and macrophage effector functions; and, a panel of 40-mer peptides, representing the CD40-interacting domain of mouse CD40L, with single substitutions resulted in altered CD40 signaling through various signaling intermediates and effector functions in mouse macrophages. We therefore construct the first-ever message encryption-decryption in a biological receptor-ligand system wherein the CD40L residues that interact with CD40 residues have encrypted messages, which are decoded by CD40 signaling to result in residue-specific effector functions. This review presents a novel perspective of receptor-ligand interaction as a system of message transmission, message decoding by signaling, and its transcription to various read-outs. [250 words].

Immunotherapy has emerged as a revolutionary cancer treatment, particularly with the introduction of immune checkpoint inhibitors (ICIs). ICIs target specific proteins that restrain the immune system from attacking cancer cells. Prominent examples of checkpoint proteins that ICIs block include PD-1, PD-L1, and CTLA-4. The success of PD-1/L1 and CTLA-4 blockade has prompted further research on other inhibitory mechanisms that could aid in the treatment of cancer. One such mechanism is the BTLA/HVEM checkpoint, which regulates immune responses in a similar manner to CTLA-4 and PD-1. BTLA, a member of the Ig superfamily, binds to HVEM, a member of the TNF receptor superfamily. While BTLA is essential for maintaining immunological self-tolerance and preventing autoimmune diseases, overexpression of BTLA and HVEM has been observed in various malignancies such as lung, ovarian, glioblastoma, gastric cancer, and non-Hodgkin's lymphoma. The function of the BTLA/HVEM checkpoint in various malignancies has been extensively studied, revealing its significant role in immunotherapy for cancer. This review study aims to explain the BTLA/HVEM checkpoint and its functions in different types of cancers. In conclusion, the development of new immunotherapies such as ICIs has revolutionized cancer treatment. The discovery of the BTLA/HVEM checkpoint and its role in various malignancies provides opportunities for advancing cancer treatment through immunotherapy.

Rattus rattus are the main carriers of various zoonotic diseases including leptospirosis. Regrettably, information underlying the cytokine response of wild R. rattus upon leptospirosis infection is lacking. This study aims to understand the immune response presented by specifically the kidney and liver of R. rattus during leptospirosis infection.