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ErpY-like protein (LIC11966) is an antigen from Leptospira spp., which is possibly involved in the infection process and, consequently, can be a promising solution for the development of new diagnostic tests and vaccines. Here, the presence of the erpY-like gene was evaluated in several Leptospira serovars by polymerase chain reaction (PCR), and the ErpY-like recombinant protein was produced and characterized in terms of antigenicity and immunogenicity in vivo. The erpY-like gene was detected by PCR in all Leptospira pathogenic serovars tested (n = 8) and was absent in the saprophytic ones. The rErpY-like protein was recognized by antibodies present in the sera of humans and animals (swine and canine) naturally infected, suggesting ErpY-like expression during natural infection. The rErpY-like protein used to immunize mice with Freund’s adjuvant stimulated a mixed Th1/Th2 response, an important protective immunity against leptospirosis

Altered redox biology challenges all cells, with compensatory responses often determining a cell's fate. When 15 lipoxygenase 1 (15LO1), a lipid-peroxidizing enzyme abundant in asthmatic human airway epithelial cells (HAECs), binds phosphatidylethanolamine-binding protein 1 (PEBP1), hydroperoxy-phospholipids, which drive ferroptotic cell death, are generated. Peroxidases, including glutathione peroxidase 4 (GPX4), metabolize hydroperoxy-phospholipids to hydroxy derivatives to prevent ferroptotic death, but consume reduced glutathione (GSH). The cystine transporter SLC7A11 critically restores/maintains intracellular GSH. We hypothesized that high 15LO1, PEBP1, and GPX4 activity drives abnormal asthmatic redox biology, evidenced by lower bronchoalveolar lavage (BAL) fluid and intraepithelial cell GSH:oxidized GSH (GSSG) ratios, to enhance type 2 (T2) inflammatory responses. GSH, GSSG (enzymatic assays), 15LO1, GPX4, SLC7A11, and T2 biomarkers (Western blot and RNA-Seq) were measured in asthmatic and healthy control (HC) cells and fluids, with siRNA knockdown as appropriate. GSSG was higher and GSH:GSSG lower in asthmatic compared with HC BAL fluid, while intracellular GSH was lower in asthma. In vitro, a T2 cytokine (IL-13) induced 15LO1 generation of hydroperoxy-phospholipids, which lowered intracellular GSH and increased extracellular GSSG. Lowering GSH further by inhibiting SLC7A11 enhanced T2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances corresponded to 15LO1 and SLC7A11 expression, T2 biomarkers, and worsened clinical outcomes. Thus, 15LO1 pathway-induced redox biology perturbations worsen T2 inflammation and asthma control, supporting 15LO1 as a therapeutic target.

BACKGROUNDSusceptibility to HIV-1 infection varies between individuals, but the biological determinants of acquisition risk remain poorly defined.METHODSWe conducted a case-control study nested within a high-risk cohort in Kenya. We compared the plasma extracellular RNA collected before HIV-1 acquisition with that from matched uninfected individuals acting as controls to identify immunological processes linked to infection risk.RESULTSIndividuals who later acquired HIV-1 exhibited upregulation of immune processes that facilitate viral infection, including T cell suppression and type II IFN and Th2 immune responses. In contrast, processes associated with antiviral defence and tissue repair, such as neutrophil and NK cell responses, type I IFN responses, wound healing, and angiogenesis, were downregulated.CONCLUSIONThese findings highlight dampened antiviral immunity prior to exposure as a correlate of increased risk for subsequent HIV-1 acquisition.FUNDINGThis work was supported by a Wellcome Trust Award (209289/Z/17/Z) and the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) through the Developing Excellence in Leadership, Training and Science in Africa (DELTAS Africa) programme (Del-22-007), which is supported by the Science for Africa Foundation; Wellcome Trust; the UK Foreign, Commonwealth & Development Office; the European Union; and the Ragon Institute of Mass General, MIT, and Harvard. The Bill & Melinda Gates Foundation, Gilead Sciences Inc., and Aidsfonds provided additional support. The US President's Emergency Plan for AIDS Relief (PEPFAR) supported the cohort study through the US Agency for International Development (USAID).

Allergic rhinitis (AR) represents a global health concern where it affects approximately 400 million people worldwide. The prevalence of AR has increased over the years along with increased urbanization and environmental pollutants thought to be some of the leading causes of the disease. Understanding the pathophysiology of AR is crucial in the development of novel therapies to treat this incurable disease that often comorbids with other airway diseases. Hence in this mini review, we summarize the well-established yet vital aspects of AR. These include the epidemiology, clinical and laboratory diagnostic criteria, AR in pediatrics, pathophysiology of AR, Th2 responses in the disease, as well as pharmacological and immunomodulating therapies for AR patients.

In a process termed trained immunity activated dendritic cells (DCs) and macrophages undergo distinct metabolic changes that contribute to their effector function: While certain activated DC subsets and M1 macrophages undergo a switch towards higher rates of glycolysis and a “disrupted Krebs cycle” to produce important immune effector molecules, alternatively activated (M2) macrophages, plasmacytoid DCs (pDCs), and conventional DCs type 1 (cDC1s) can rely on oxidative phosphorylation for their effector function. DCs and macrophages are also important cells in allergic reactions. While the induction of trained immune responses by microbial stimuli and vaccines is meanwhile well characterized, the contribution of trained immunity to either the establishment, elicitation, or treatment of allergic responses is largely unknown. In this context, recent results suggest distinct trained immunity responses to be established in allergic children. Here it seems that infections early in life predispose to the latter development of allergies, and trained immunity to also contribute to the immune modulation occurring in allergic patients during allergen-specific immunotherapy. Therefore, better understanding of trained immunity in these antigen-presenting cell (APC) subsets may allow to establish new biomarkers and enable a more targeted and efficient treatment of allergic diseases. This article summarizes the specific immune metabolic alterations observed in activated DCs and macrophages explaining their connection to DC and macrophage effector function. It then discusses our current knowledge on the contribution of trained immune responses in the establishment and treatment of allergic diseases.

IL-22 has both proinflammatory and antiinflammatory properties. Its role in allergic lung inflammation has not been explored. To investigate the expression and roles of IL-22 in the onset and resolution of experimental allergic asthma and its cross-talk with IL-17A. IL-22 expression was assessed in patient samples and in the lung of mice immunized and challenged with ovalbumin. IL-22 functions in allergic airway inflammation were evaluated using mice deficient in IL-22 or anti-IL-22 neutralizing antibodies. Moreover, the effects of recombinant IL-22 and IL-17A neutralizing antibodies were investigated. Increased pulmonary IL-22 expression is found in the serum of patients with asthma and mice immunized and challenged with ovalbumin. Allergic lung inflammation is IL-22 dependent because eosinophil recruitment, Th2 cytokine including IL-13 and IL-33, chemokine production, airway hyperreactivity, and mucus production are drastically reduced in mice deficient in IL-22 or by IL-22 antibody neutralization during immunization of wild-type mice. By contrast, IL-22 neutralization during antigen challenge enhanced allergic lung inflammation with increased Th2 cytokines. Consistent with this, recombinant IL-22 given with allergen challenge protects mice from lung inflammation. Finally, IL-22 may regulate the expression and proinflammatory properties of IL-17A in allergic lung inflammation. IL-22 is required for the onset of allergic asthma, but functions as a negative regulator of established allergic inflammation. Our study reveals that IL-22 contributes to the proinflammatory properties of IL-17A in experimental allergic asthma.

The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters. Th2-driven (IL-4/IL-13) airway diseases, such as asthma, cause goblet cell metaplasia, accompanied by increased mucus production and airway secretions. In this study, we investigate the effect of IL-13 on chloride and liquid transport performed by ionocytes. IL-13 treatment of human airway epithelia was associated with reduced epithelial liquid absorption rates and increased ASL volume. Additionally, IL-13 treatment reduced the abundance of CFTR-positive ionocytes and increased the abundance of CFTR-positive secretory cells. Increasing ionocyte abundance attenuated liquid secretion caused by IL-13. Finally, CFTR-positive ionocytes were less common in asthma and chronic obstructive pulmonary disease and were associated with airflow obstruction. Our findings suggest that loss of CFTR in ionocytes contributes to the liquid secretion observed in IL-13-mediated airway diseases.

Eosinophils are granulocytes primarily associated with TH2 responses to parasites or immune hyper-reactive states, such as asthma, allergies, or eosinophilic esophagitis. However, it does not make sense from an evolutionary standpoint to maintain a cell type that is only specific for parasitic infections and that otherwise is somehow harmful to the host. In recent years, there has been a shift in the perception of these cells. Eosinophils have recently been recognized as regulators of immune homeostasis and suppressors of over-reactive pro-inflammatory responses by secreting specific molecules that dampen the immune response. Their role during parasitic infections has been well investigated, and their versatility during immune responses to helminths includes antigen presentation as well as modulation of T cell responses. Although it is known that eosinophils can present antigens during viral infections, there are still many mechanistic aspects of the involvement of eosinophils during viral infections that remain to be elucidated. However, are eosinophils able to respond to bacterial infections? Recent literature indicates that Helicobacter pylori triggers TH2 responses mediated by eosinophils; this promotes anti-inflammatory responses that might be involved in the long-term persistent infection caused by this pathogen. Apparently and on the contrary, in the respiratory tract, eosinophils promote TH17 pro-inflammatory responses during Bordetella bronchiseptica infection, and they are, in fact, critical for early clearance of bacteria from the respiratory tract. However, eosinophils are also intertwined with microbiota, and up to now, it is not clear if microbiota regulates eosinophils or vice versa, or how this connection influences immune responses. In this review, we highlight the current knowledge of eosinophils as regulators of pro and anti-inflammatory responses in the context of both infection and naïve conditions. We propose questions and future directions that might open novel research avenues in the future.

Autophagy, host immune responses, and macrophage polarization form a tightly regulated network. This network significantly influences the outcome of intracellular pathogenic infections. Autophagy acts as a critical cellular defense mechanism. It degrades intracellular pathogens and helps with antigen presentation in antigen presenting cells like macrophages. Intracellular parasites have evolved diverse strategies to modulate autophagy. They may inhibit autophagosome formation, block autophagosome-lysosome fusion, or redirect autophagic flux for their survival. These manipulations allow pathogens to evade degradation and persist within host cells. Macrophage polarization further influences autophagic activity: M1 macrophages typically exhibit enhanced autophagy, supporting antimicrobial functions, while M2 macrophages show reduced autophagic flux, contributing to immune regulation and tissue repair. Autophagy itself can influence macrophage phenotypes, with its activation promoting M1-like characteristics and its inhibition favoring M2-like responses. The macrophage polarization states influence T cell polarization and infection outcome. This bidirectional relationship between autophagy and macrophage polarization plays a pivotal role in determining host resistance or susceptibility to intracellular pathogens. In this review, we highlight findings from macrophage-infecting pathogens that manipulate autophagy, macrophage and T cell to enhance their survival within the host.

Imperatorin is a furanocoumarin derivative and an effective ingredient in several Chinese medicinal herbs. It has favorable expectorant, analgesic, and anti-inflammatory effects. In this study, we investigated whether imperatorin has protective effects against Dermatophagoides pteronyssinus (Der p)-induced asthma in mice. Lung and bronchial tissues were histopathologically examined through hematoxylin–eosin staining. The concentrations of immunoglobin E (IgE), IgG1, IgG2a in serum and those of T helper 1 (Th1) and two cytokines and eosinophil-activated chemokines in bronchoalveolar lavage fluid (BALF) were detected using an enzyme immunoassay. Histological examination revealed that imperatorin reduced inflammatory cell infiltration, mucus hypersecretion, and endothelial cell hyperplasia. The examination also indicated that imperatorin could reduce the inflammatory cell count in BALF as well as IgE and IgG1 expression in serum, but IgG2a expression was significantly increased. Imperatorin reduced the production of interleukin (IL)-4, IL-5, and IL-13 by Th2, promoted the production of interferon-γ and IL-12 by Th1, and increased the production of IL-10 in bronchoalveolar lavage fluid. These findings suggest that imperatorin has a considerable anti-inflammatory effect on Der p-induced allergic asthma in mice.