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Klebsiella pneumoniae , particularly hypervirulent strains (hv Kp ), poses a critical public health threat due to its capacity to cause severe, rapidly progressing infections such as pneumonia and sepsis, often leading to acute lung injury (ALI) and high mortality. Despite the recognized role of excessive inflammation and cytokine storms in hv Kp pathogenesis, the precise mechanisms linking immune hyperactivation to fatal tissue damage remain poorly defined. This study reveals that hv Kp infection triggers a coordinated form of inflammatory cell death, PANoptosis, in AMs, the frontline immune defenders in the lungs. We identify the transcription factor STAT1 as a central regulator of this process, driven by a synergistic cytokine milieu, especially involving IFN-γ. Our findings establish a direct mechanistic pathway from hv Kp -induced cytokine release to STAT1-mediated PANoptosis, macrophage depletion, and subsequent lung failure. This work not only advances the understanding of hv Kp virulence but also highlights host signaling pathways and specific cytokines as potential therapeutic targets to modulate immunopathology and improve outcomes in severe Klebsiella infections.

HIV-1 primarily targets two groups of cells in vivo : CD4 + T lymphocytes and myeloid lineage cells, such as macrophages and dendritic cells. Although myeloid cells are more resistant to HIV-1 infection than CD4 + T cells, some cytokines, including interleukin (IL)-4 and IL-6, promote myeloid cell infection. Gap junction protein beta 2 (GJB2) is particularly relevant in the field of auditory science. Here, we identified GJB2 as a novel antiviral factor by demonstrating that IL-4-mediated reduction in GJB2 levels enhanced HIV-1 infection in myeloid cells. Interestingly, GJB2 expression was regulated by IL-4 but not by interferons. The reduction in GJB2 levels was inversely correlated with increased HIV-1 infection levels, suggesting the potential of GJB2 for combating HIV/AIDS.

Anti-cytokine autoantibodies represent an expanding field in immunology, and their study has revealed crucial insights into immune cell dysfunction. These autoantibodies are now classified by the International Union of Immunological Societies (IUIS) as phenocopies of primary immunological deficiencies within the broader category of inborn immunity defects. Indeed, the critical importance of these autoantibodies became starkly apparent during the COVID-19 pandemic when patients with type I interferon autoantibodies showed significantly higher rates of severe illness. This review examines how neutralizing autoantibodies, exemplified by those targeting granulocyte monocyte stimulating factor, can compromise immune function in otherwise immunocompetent individuals, making them more susceptible to specific fungal and bacterial infections. This understanding highlights the crucial role of anti-cytokine antibodies in infection susceptibility and immune system regulation.

The severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects of genistein, a natural isoflavone present in soybeans, on C. albicans. The genistein-treated C. albicans cells were then exposed to macrophages. Although no inhibition effect on the growth rates of C. albicans was noted an enhancement of the immune response to macrophages has been observed, indicated by phagocytosis and release of cytokines TNF-α and IL-10. The effect of genistein on the enhanced phagocytosis can be mimicked by the fungicides fludioxonil or iprodione, which inhibit the histidine kinase Cos1p and lead to activation of HOG pathway. The western blot results showed a clear phosphorylation of Hog1p in the wild type strain of C. albicans after incubation with genistein. In addition, effects of genistein on the phosphorylation of Hog1p in the histidine kinase mutants Δcos1 and Δsln1 were also observed. Our results thus indicate a new bio-activity of genistein on C. albicans by activation of the HOG pathway of the human pathogen C. albicans.

Mycobacterial diseases are a major public health challenge. Their causative agents include, in order of impact, members of the Mycobacterium tuberculosis complex (causing tuberculosis), Mycobacterium leprae (causing leprosy), and non-tuberculous mycobacterial pathogens including Mycobacterium ulcerans. Macrophages are mycobacterial targets and they play an essential role in the host immune response to mycobacteria. This review aims to provide a comprehensive understanding of the immune-metabolic adaptations of the macrophage to mycobacterial infections. This metabolic rewiring involves changes in glycolysis and oxidative metabolism, as well as in the use of fatty acids and that of metals such as iron, zinc and copper. The macrophage metabolic adaptations result in changes in intracellular metabolites, which can post-translationally modify proteins including histones, with potential for shaping the epigenetic landscape. This review will also cover how critical tuberculosis co-morbidities such as smoking, diabetes and HIV infection shape host metabolic responses and impact disease outcome. Finally, we will explore how the immune-metabolic knowledge gained in the last decades can be harnessed towards the design of novel diagnostic and therapeutic tools, as well as vaccines.