Differential recognition of HIV-stimulated IL-1β and IL-18 secretion through NLR and NAIP signalling in monocyte-derived macrophages

Macrophages are important drivers of pathogenesis and progression to AIDS in HIV infection. The virus in the later phases of the infection is often predominantly macrophage-tropic and this tropism contributes to a chronic inflammatory and immune activation state that is observed in HIV patients. Pattern recognition receptors of the innate immune system are the key molecules that recognise HIV and mount the inflammatory responses in macrophages. The innate immune response against HIV-1 is potent and elicits caspase-1-dependent pro-inflammatory cytokine production of IL-1β and IL-18. Although, NLRP3 has been reported as an inflammasome sensor dictating this response little is known about the pattern recognition receptors that trigger the “priming” signal for inflammasome activation, the NLRs involved or the HIV components that trigger the response. Using a combination of siRNA knockdowns in monocyte derived macrophages (MDMs) of different TLRs and NLRs as well as chemical inhibition, it was demonstrated that HIV Vpu could trigger inflammasome activation via TLR4/NLRP3 leading to IL-1β/IL-18 secretion. The priming signal is triggered via TLR4, whereas the activation signal is triggered by direct effects on Kv1.3 channels, causing K+ efflux. In contrast, HIV gp41 could trigger IL-18 production via NAIP/NLRC4, independently of priming, as a one-step inflammasome activation. NAIP binds directly to the cytoplasmic tail of HIV envelope protein gp41 and represents the first non-bacterial ligand for the NAIP/NLRC4 inflammasome. These divergent pathways represent novel targets to resolve specific inflammatory pathologies associated with HIV-1 infection in macrophages.

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microRNA-210 and microRNA-3570 Negatively Regulate NF-κB-Mediated Inflammatory Responses by Targeting RIPK2 in Teleost Fish

Frontiers in Immunology ◽

10.3389/fimmu.2021.617753 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hui Su ◽

Renjie Chang ◽

Weiwei Zheng ◽

Yuena Sun ◽

Tianjun Xu

Keyword(s):

Immune Response ◽

Signaling Pathway ◽

Innate Immune Response ◽

Inflammatory Responses ◽

Innate Immune ◽

Regulatory Role ◽

Inflammatory Cytokine Production ◽

Immune Genes ◽

Lower Vertebrates ◽

Antimicrobial Immunity

Pathogen infection can cause the production of inflammatory cytokines, which are key mediators that cause the host’s innate immune response. Therefore, proper regulation of immune genes associated with inflammation is essential for immune response. Among them, microRNAs (miRNAs) as gene regulator have been widely reported to be involved in the innate immune response of mammals. However, the regulatory network in which miRNAs are involved in the development of inflammation is largely unknown in lower vertebrates. Here, we identified two miRNAs from miiuy croaker (Miichthys miiuy), miR-210 and miR-3570, which play a negative regulatory role in host antibacterial immunity. We found that the expressions of miR-210 and miR-3570 were significantly upregulated under the stimulation of Gram-negative bacterium vibrio harveyi and LPS (lipopolysaccharide). Induced miR-210 and miR-3570 inhibit inflammatory cytokine production by targeting RIPK2, thereby avoiding excessive inflammation. In particular, we found that miR-210 and miR-3570 negatively regulate antimicrobial immunity by regulating the RIPK2-mediated NF-κB signaling pathway. The collective results indicated that both miRNAs are used as negative feedback regulators to regulate RIPK2-mediated NF-κB signaling pathway and thus play a regulatory role in bacteria-induced inflammatory response.

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HIV-1 and pattern-recognition receptors: a marriage of convenience

Nature Immunology ◽

10.1038/ni0510-363 ◽

2010 ◽

Vol 11 (5) ◽

pp. 363-365 ◽

Cited By ~ 5

Author(s):

Michel J Tremblay

Keyword(s):

Pattern Recognition ◽

Pattern Recognition Receptors ◽

Hiv 1

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Pattern recognition receptors and their roles in the host response to Helicobacter pylori infection

Future Microbiology ◽

10.2217/fmb-2021-0106 ◽

2021 ◽

Author(s):

Ileana Gonzalez ◽

Paulina Araya ◽

Ivan Schneider ◽

Cristian Lindner ◽

Armando Rojas

Keyword(s):

Pattern Recognition ◽

Helicobacter Pylori ◽

Host Response ◽

Pattern Recognition Receptors ◽

Innate Immune ◽

Host Cells ◽

Proinflammatory Response ◽

H Pylori ◽

Cancer Pattern ◽

Main Pattern

Helicobacter pylori ( H. pylori) infection is highly prevalent, affecting 4.4 billion people globally. This pathogen is a risk factor in the pathogenesis of more than 75% of worldwide cases of gastric cancer. Pattern recognition receptors are essential in the innate immune response to H. pylori infection. They recognize conserved pathogen structures and myriad alarmins released by host cells in response to microbial components, cytokines or cellular stress, thus triggering a robust proinflammatory response, which is crucial in H. pylori-induced gastric carcinogenesis. In this review, we intend to highlight the main pattern recognition receptors involved in the recognition and host response to H. pylori, as well as the main structures recognized and the subsequent inflammatory response.

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Innate Immune Pattern Recognition Receptors of Mycobacterium tuberculosis: Nature and Consequences for Pathogenesis of Tuberculosis

10.1007/978-3-030-67452-6_9 ◽

2021 ◽

pp. 179-215

Author(s):

Anthony G. Tsolaki ◽

Praveen Mathews Varghese ◽

Uday Kishore

Keyword(s):

Pattern Recognition ◽

Mycobacterium Tuberculosis ◽

Pattern Recognition Receptors ◽

Innate Immune

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Diverse Functions of Pulmonary Collectins in Host Defense of the Lung

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/532071 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 22

Author(s):

Shigeru Ariki ◽

Chiaki Nishitani ◽

Yoshio Kuroki

Keyword(s):

Pattern Recognition ◽

Growth Inhibition ◽

Host Defense ◽

Pulmonary Surfactant ◽

Inflammatory Responses ◽

Biological Activities ◽

Innate Immune ◽

The Other ◽

Surfactant Proteins ◽

Specific Proteins

Pulmonary surfactant is a mixture of lipids and proteins that covers alveolar surfaces and keeps alveoli from collapsing. Four specific proteins have been identified in surfactant. Among them, two C-type lectins, surfactant proteins A and D (SP-A and SP-D), are known to be implicated in host defense and regulation of inflammatory responses of the lung. These host defense lectins are structurally characterized by N-terminal collagen-like domains and lectin domains and are called pulmonary collectins. They prevent dissemination of infectious microbes by their biological activities including agglutination and growth inhibition. They also promote clearance of microbes by enhancing phagocytosis in macrophages. In addition, they interact with the other pattern-recognition molecules, including Toll-like receptors (TLRs) and TLR-associated molecules, CD14 and MD-2, and regulate inflammatory responses. Furthermore, recent studies have demonstrated that these collectins modulate functions of neutrophil-derived innate immune molecules by interacting with them. These findings indicate that pulmonary collectins play critical roles in host defense of the lung.

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Early Innate Immune Responses to Sin Nombre Hantavirus Occur Independently of IFN Regulatory Factor 3, Characterized Pattern Recognition Receptors, and Viral Entry

The Journal of Immunology ◽

10.4049/jimmunol.179.3.1796 ◽

2007 ◽

Vol 179 (3) ◽

pp. 1796-1802 ◽

Cited By ~ 35

Author(s):

Joseph B. Prescott ◽

Pamela R. Hall ◽

Virginie S. Bondu-Hawkins ◽

Chunyan Ye ◽

Brian Hjelle

Keyword(s):

Pattern Recognition ◽

Immune Responses ◽

Viral Entry ◽

Pattern Recognition Receptors ◽

Innate Immune ◽

Innate Immune Responses ◽

Regulatory Factor

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Mitochondrial Regulation of Inflammasome Activation in Chronic Obstructive Pulmonary Disease

Journal of Innate Immunity ◽

10.1159/000441299 ◽

2015 ◽

Vol 8 (2) ◽

pp. 121-128 ◽

Cited By ~ 7

Author(s):

Chang Min Yoon ◽

Milang Nam ◽

Yeon-Mok Oh ◽

Charles S. Dela Cruz ◽

Min-Jong Kang

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Inflammatory Responses ◽

Pulmonary Inflammation ◽

Innate Immune ◽

Western Society ◽

Future Research ◽

Chronic Obstructive ◽

Inflammasome Activation ◽

Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by enhanced chronic airway and lung inflammatory responses to noxious particles or gases. It is a major unmet medical need worldwide, and in Western society is strongly associated with exposure to cigarette smoke (CS). CS-induced inflammation is believed to be a key immune driver in the pathogenesis of COPD. Since the concept of inflammasomes was first introduced nearly a decade ago, these have been increasingly recognized as a central player in innate immune and inflammatory responses. In addition, studies have emerged demonstrating that mitochondrial innate immune signaling plays an important role in CS-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. Here, recent discoveries about inflammasome activation and mitochondrial biology and their role in COPD pathogenesis are reviewed. In addition, the current limitations of our understanding of this theme and future research directions are discussed.

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