bims-inflin 2024-01-14 papers

Issue of 2024‒01‒14
three papers selected by
Juliane Cristina Ribeiro Fernandes, Faculdade de Medicina de Ribeirão Preto

iScience. 2024 Jan 19. 27(1): 108620

Aedes aegypti saliva modulates inflammasome activation and facilitates flavivirus infection in vitro.

Gaurav Shrivastava, Paola Carolina Valenzuela-Leon, Karina Botello, Eric Calvo.

Mosquito borne flaviviruses such as dengue and Zika represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Vertebrate host responses to dengue and Zika infections include the processing and release of pro-inflammatory cytokines through the activation of inflammasomes, resulting in disease severity and fatality. Mosquito saliva can facilitate pathogen infection by downregulating the host's immune response. However, the role of mosquito saliva in modulating host innate immune responses remains largely unknown. Here, we show that mosquito salivary gland extract (SGE) inhibits dengue and Zika virus-induced inflammasome activation by reducing NLRP3 expression, Caspase-1 activation, and 1L-1β secretion in cultured human and mice macrophages. As a result, we observe that SGE inhibits virus detection in the early phase of infection. This study provides important insights into how mosquito saliva modulates host innate immunity during viral infection.

Keywords: Biological sciences; Natural sciences; Virology

DOI: https://doi.org/10.1016/j.isci.2023.108620

Mycoses. 2024 Jan;67(1): e13680

NLRP3 regulates CIITA/MHC II axis and interferon-γ-inducible chemokines in Malassezia globosa-infected keratinocytes.

Yun Luo, Jin-Feng Tang, Fei-Fei Gao, Juan-Hua Quan, Chuan-Ting Ma, Shi-Jie Li, Yi-Ming Fan.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1β and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.

Keywords: Malassezia ; CIITA; HaCaT cell; MHC II; NLRP3 inflammasome; mice

DOI: https://doi.org/10.1111/myc.13680

Cell Commun Signal. 2024 Jan 09. 22(1): 22

cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation.

Jingwen Liu, Jing Zhou, Yuling Luan, Xiaoying Li, Xiangrui Meng, Wenhao Liao, Jianyuan Tang, Zheilei Wang.

BACKGROUND: Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression and organ degeneration, but the mechanism and regulation of the crosstalk network remain unclear. Cellular stress disrupts mitochondrial homeostasis, facilitates the opening of mitochondrial permeability transition pore and the leakage of mitochondrial DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, and subsequently induces inflammasomes activation and the onset of pyroptosis. Meanwhile, the inflammasome-associated protein caspase-1, Gasdermin D, the CARD domain of ASC and the potassium channel are involved in regulating cGAS-STING pathway. Importantly, this crosstalk network has a cascade amplification effect that exacerbates the immuno-inflammatory response, worsening the pathological process of inflammatory and autoimmune diseases. Given the importance of this crosstalk network of cGAS-STING, inflammasomes and pyroptosis in the regulation of innate immunity, it is emerging as a new avenue to explore the mechanisms of multiple disease pathogenesis. Therefore, efforts to define strategies to selectively modulate cGAS-STING, inflammasomes and pyroptosis in different disease settings have been or are ongoing. In this review, we will describe how this mechanistic understanding is driving possible therapeutics targeting this crosstalk network, focusing on the interacting or regulatory proteins, pathways, and a regulatory mitochondrial hub between cGAS-STING, inflammasomes, and pyroptosis.SHORT CONCLUSION: This review aims to provide insight into the critical roles and regulatory mechanisms of the crosstalk network of cGAS-STING, inflammasomes and pyroptosis, and to highlight some promising directions for future research and intervention.

Keywords: Crosstalk network; Diseases; Inflammasome; Inflammation; Pyroptosis; cGAS-STING

DOI: https://doi.org/10.1186/s12964-023-01466-w