A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis.

Invasive Aspergillosis (IA), typically caused by the fungus , is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment of infection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts.

Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.

Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive evolutionary downregulation of pathogen-sensing inflammasome pathways in Carnivora.

Flagellin Activates NAIP/NLRC4 and Canonical NLRP3 Inflammasomes in Human Macrophages.

Infection of human macrophages with serovar Typhimurium ( Typhimurium) leads to inflammasome activation. Inflammasomes are multiprotein complexes facilitating caspase-1 activation and subsequent gasdermin D-mediated cell death and IL-1β and IL-18 cytokine release. The NAIP/NLRC4 inflammasome is activated by multiple bacterial protein ligands, including flagellin from the flagellum and the needle protein PrgI from the Typhimurium type III secretion system.

Macrophage reprogramming for therapy.

Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control.

NLR in eXile: Emerging roles of NLRX1 in immunity and human disease.

NLRX1 is a member of the NOD-like receptor family, a set of pattern recognition receptors associated with innate immunity. Interestingly, NLRX1 exists in somewhat of an exile from its NLR counterparts with unique features that mediate atypical functions compared with traditional NOD-like receptors (NLRs). Aside from a mitochondrial targeting sequence, the N-terminal region is yet to be characterized.

Tissue-resident macrophages actively suppress IL-1beta release via a reactive prostanoid/IL-10 pathway.

The alarm cytokine interleukin-1β (IL-1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1β production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1β; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL-1β from its pro-form. However, despite the important role of IL-1β in controlling local and systemic inflammation, its overall regulation is still not fully understood.