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The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. has been shown to be a powerful model for studying the mechanism of innate immunity and host-pathogen interactions because and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in will help us better study human innate immunity-related diseases.
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http://dx.doi.org/10.3389/fimmu.2022.905370 | DOI Listing |
Natl Sci Rev
September 2025
School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
The role of cholesterol metabolism in antiviral immunity has been established, but if and how this cholesterol-mediated immunometabolism can be regulated by specific small molecules is of particular interest in the quest for novel antiviral therapeutics. Here, we first demonstrate that NPC1 is the key cholesterol transporter for suppressing viral replication by changing cholesterol metabolism and triggering the innate immune response via systemic analyses of all possible cholesterol transporters. We then use the Connectivity Map (CMap), a systematic methodology for identifying functional connections between genetic perturbations and drug actions, to screen NPC1 inhibitors, and found that bis-benzylisoquinoline alkaloids (BBAs) exhibit high efficacy in the inhibition of viral infections.
View Article and Find Full Text PDFImmunooncol Technol
September 2025
Division of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Background: Breast cancer is a systemic disease, yet the impact of tumor molecular subtype and disease stage on the systemic immune landscape remains poorly understood. In this study, we comprehensively analyzed the systemic immune landscape in a large cohort of breast cancer patients, encompassing all molecular subtypes and disease stages, alongside a control group of healthy donors.
Materials And Methods: Using multi-parameter flow cytometry, we assessed the abundance, phenotype, and activation status of diverse innate and adaptive immune cell populations across peripheral blood samples from 355 breast cancer patients and 65 healthy donors.
Cell Physiol Biochem
September 2025
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biochemistry, 10117 Berlin, Germany.
Background/aims: The ubiquitin-like protein ISG15 and its covalent conjugation to substrates (ISGylation) represent a critical interferon (IFN)-induced antiviral mechanism. USP18 is an ISG15-specific isopeptidase and a key negative regulator of type I IFN signaling. While inactivation of USP18's catalytic activity enhances ISGylation and promotes viral resistance, its role in modulating inflammation and cardiac function during CVB3-induced myocarditis remains unclear.
View Article and Find Full Text PDFCell Immunol
September 2025
Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:
Both trained immunity (TRIM) and endotoxin tolerance (ET) initiate similar metabolic reprogramming characterized by enhanced glycolysis following an initial stimulus. However, TRIM exhibited heightened immune activation upon restimulation, whereas ET showed suppressed innate immune response. This divergence is attributed to distinct metabolic intermediates accumulated after the initial stimulation.
View Article and Find Full Text PDFCell Mol Immunol
September 2025
Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University; Frontier Science Center for Immunology; Taikang Center for Life and Medical Sciences; State Key Laboratory of Virology; Institute of Hepatobiliary Diseases of Wuhan University, Wuhan, Hubei, 430071,
Upon DNA virus infection, cGAS senses viral DNA and triggers MITA (also called STING)-dependent induction of type I interferons (IFN-Is) and other cytokines/chemokines. IFN-Is further activate STAT1/2 to induce interferon-stimulated genes (ISGs) and the innate antiviral response. How the innate antiviral response is silenced in uninfected cells and efficiently mounts upon viral infection is not fully understood.
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