The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling.

Background And Purpose: Fibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral-fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza-induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral-mediated fibrotic remodelling.

Obesity exacerbates influenza-induced respiratory disease via the arachidonic acid-p38 MAPK pathway.

Obesity is a risk factor for severe influenza, and asthma exacerbations caused by respiratory viral infections. We investigated mechanisms that increase the severity of airway disease related to influenza in obesity using cells derived from obese and lean individuals, and and models. Primary human nasal epithelial cells (pHNECs) derived from obese compared with lean individuals developed increased inflammation and injury in response to influenza A virus (IAV).

Common pathogen-associated molecular patterns induce the hyper-activation of NLRP3 inflammasome in circulating B lymphocytes of HIV-infected individuals.

Objective: Despite the antiretroviral treatment, people with HIV (PWH) still experience systemic chronic inflammation and immune-senescence, which represent risk factors for severe comorbidities and inefficient response to pathogens and vaccines. Given the dysregulation of NLRP3 inflammasome in PWH and the recently demonstrated role played by NLRP3 in B lymphocytes, we hypothesized that NLRP3 dysregulation in B cells can contribute to chronic inflammation and humoral dysfunction in PWH.

Design: NLRP3 inflammasome activation was evaluated in B lymphocytes and correlated with antibodies production and immunization response in PWH.

Inflammatory effect of Bothropstoxin-I from Bothrops jararacussu venom mediated by NLRP3 inflammasome involves ATP and P2X7 receptor.

Muscle tissue damage is one of the local effects described in bothropic envenomations. Bothropstoxin-I (BthTX-I), from Bothrops jararacussu venom, is a K49-phospholipase A2 (PLA2) that induces a massive muscle tissue injury, and, consequently, local inflammatory reaction. The NLRP3 inflammasome is a sensor that triggers inflammation by activating caspase 1 and releasing interleukin (IL)-1β and/or inducing pyroptotic cell death in response to tissue damage.

Sensing soluble uric acid by Naip1-Nlrp3 platform.

Uric acid (UA), a product of purine nucleotide degradation able to initiate an immune response, represents a breakpoint in the evolutionary history of humans, when uricase, the enzyme required for UA cleavage, was lost. Despite being inert in human cells, UA in its soluble form (sUA) can increase the level of interleukin-1β (IL-1β) in murine macrophages. We, therefore, hypothesized that the recognition of sUA is achieved by the Naip1-Nlrp3 inflammasome platform.

Inflammasome genetics and complex diseases: a comprehensive review.

The inflammasome is a cytoplasmic multiprotein complex responsible for the activation of inflammatory caspases (caspase-1, -4, and -5) in response to pathogen- and/or damage-associated molecular patterns or to homeostasis-altering molecular pathways, and for the consequent release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Taking in account the complexity of inflammasome activation and that several regulatory steps are involved in maintaining its physiologic role in homeostasis and innate immune response, it does not surprise that several genetic variants in inflammasome components have been associated with common pathologies in the general population, such as autoimmune disorders, cardiovascular diseases, obesity and associated metabolic syndrome, neurodegenerative diseases, and cancer. Moreover, the susceptibility to infectious agents and/or to develop severe complications during infections also has been related to inflammasome genetics.

Flagellin/NLRC4 Pathway Rescues NLRP3-Inflammasome Defect in Dendritic Cells From HIV-Infected Patients: Perspective for New Adjuvant in Immunocompromised Individuals.

NLRP3 inflammasome plays a key role in dendritic cells (DC) activation in response to vaccine adjuvants, however we previously showed that it is not properly activated in DC from HIV-infected patients (HIV-DC), explaining, at least in part, the poor response to immunization of these patients. Taking in account that several cytoplasmic receptors are able to activate inflammasome, and that bacterial components are considered as a novel and efficient adjuvant, we postulated that bacterial flagellin (FLG), a natural ligand of NAIP/NLRC4 inflammasome, could rescue the activation of the complex in HIV-DC. Demonstrate that FLG is able to activate monocyte-derived dendritic cells from HIV-infected individuals better than LPS, and to what extent the entity of inflammasome activation differs between DC from HIV-infected patients and healthy donors.

The Syk-Coupled C-Type Lectin Receptors Dectin-2 and Dectin-3 Are Involved in Recognition by Human Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs), which have been extensively studied in the context of the immune response to viruses, have recently been implicated in host defense mechanisms against fungal infections. Nevertheless, the involvement of human pDCs during paracoccidioidomycosis (PCM), a fungal infection endemic to Latin America, has been scarcely studied. However, pDCs were found in the cutaneous lesions of PCM patients, and in pulmonary model of murine PCM these cells were shown to control disease severity.

Polymorphisms in SIGLEC1 contribute to susceptibility to pulmonary active tuberculosis possibly through the modulation of IL-1ß.

Siglec-1/CD169 is a sialoadhesin expressed by macrophages thought to function in cell-to-cell interactions. In the lung, the expression of Siglec-1 is specific for alveolar macrophages and single nucleotide polymorphisms (SNPs) in SIGLEC1 have been recently associated with asthma severity. Taking in account the role of alveolar macrophages in the control of M.

Alleles of HLA-DRB1*04 Associated with Pulmonary Tuberculosis in Amazon Brazilian Population.

Immunogenetic host factors are associated with susceptibility or protection to tuberculosis (TB). Strong associations of HLA class II genes with TB are reported. We analyzed the HLA-DRB1*04 alleles to identify subtypes associated with pulmonary TB and their interaction with risk factors such as alcohol, smoking, and gender in 316 pulmonary TB patients and 306 healthy individuals from the Brazilian Amazon.