NAIP/NLRC4 inflammasome participates in macrophage responses to by a mechanism that relies on cathepsin-dependent caspase-1 cleavage.

Inflammasomes are large protein complexes that, once activated, initiate inflammatory responses by activating the caspase-1 protease. They play pivotal roles in host defense against pathogens. The well-established role of NAIP/NLRC4 inflammasome in bacterial infections involves NAIP proteins functioning as sensors for their ligands.

The endoplasmic reticulum stress sensor IRE1α modulates macrophage metabolic function during infection.

Endoplasmic reticulum (ER) stress plays a major role in several inflammatory disorders. ER stress induces the unfolded protein response (UPR), a conserved response broadly associated with innate immunity and cell metabolic function in various scenarios. , an intracellular pathogen, triggers the UPR Stimulator of interferon genes (STING), an important regulator of macrophage metabolism during infection.

Gluconeogenesis: Adding a new piece to the puzzle of malaria parasitism.

Disorders of carbohydrate metabolism, including hypoglycemia and lactic acidosis, are common features of malaria. In this issue of Cell Metabolism, Ramos et al. report that regulation of gluconeogenesis and glycemia by the host glucose-6-phosphatase catalytic subunit 1 (G6Pc1) is a key metabolic step that affects both Plasmodium replication and clinical outcome of disease.

Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection.

Chagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8 T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response.

Frontline Science: Autophagy is a cell autonomous effector mechanism mediated by NLRP3 to control Trypanosoma cruzi infection.

Autophagy and inflammasome activation are cell-autonomous and cross-regulated processes involved in host resistance against infections. Our group previously described that NLRP3 inflammasome is required for the control of Trypanosoma cruzi, the causative agent of Chagas disease. However, the involvement of autophagy in this process was unclear.

The impairment in the NLRP3-induced NO secretion renders astrocytes highly permissive to T. cruzi replication.

Trypanossoma cruzi (T. cruzi), the causative protozoan of Chagas disease (CD) invades many cell types, including central nervous system (CNS) cells triggering local lesions and neurological impact. Previous work from our group described NLRP3 inflammasomes as central effectors for the parasite control by macrophages.

NLRP3 controls Trypanosoma cruzi infection through a caspase-1-dependent IL-1R-independent NO production.

Trypanosoma cruzi (T. cruzi) is an intracellular protozoan parasite and the etiological agent of Chagas disease, a chronic infectious illness that affects millions of people worldwide. Although the role of TLR and Nod1 in the control of T.

Cytosolic flagellin-induced lysosomal pathway regulates inflammasome-dependent and -independent macrophage responses.

NAIP5/NLRC4 (neuronal apoptosis inhibitory protein 5/nucleotide oligomerization domain-like receptor family, caspase activation recruitment domain domain-containing 4) inflammasome activation by cytosolic flagellin results in caspase-1-mediated processing and secretion of IL-1β/IL-18 and pyroptosis, an inflammatory cell death pathway. Here, we found that although NLRC4, ASC, and caspase-1 are required for IL-1β secretion in response to cytosolic flagellin, cell death, nevertheless, occurs in the absence of these molecules. Cytosolic flagellin-induced inflammasome-independent cell death is accompanied by IL-1α secretion and is temporally correlated with the restriction of Salmonella Typhimurium infection.