bims-inflin 2024-11-17 papers

Issue of 2024‒11‒17
three papers selected by
Juliane Cristina Ribeiro Fernandes, Faculdade de Medicina de Ribeirão Preto

Commun Biol. 2024 Nov 12. 7(1): 1494

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.

Fei-Ju Li, Lora Starrs, Anukriti Mathur, Daniel Enosi Tuipulotu, Si Ming Man, Gaetan Burgio.

Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection.

DOI: https://doi.org/10.1038/s42003-024-07204-3

Nat Commun. 2024 Nov 13. 15(1): 9835

Post-translational toxin modification by lactate controls Staphylococcus aureus virulence.

Yanan Wang, Yanfeng Liu, Guoxiu Xiang, Ying Jian, Ziyu Yang, Tianchi Chen, Xiaowei Ma, Na Zhao, Yingxin Dai, Yan Lv, Hua Wang, Lei He, Bisheng Shi, Qian Liu, Yao Liu, Michael Otto, Min Li.

Diverse post-translational modifications have been shown to play important roles in regulating protein function in eukaryotes. By contrast, the roles of post-translational modifications in bacteria are not so well understood, particularly as they relate to pathogenesis. Here, we demonstrate post-translational protein modification by covalent addition of lactate to lysine residues (lactylation) in the human pathogen Staphylococcus aureus. Lactylation is dependent on lactate concentration and specifically affects alpha-toxin, in which a single lactylated lysine is required for full activity and virulence in infection models. Given that lactate levels typically increase during infection, our results suggest that the pathogen can use protein lactylation as a mechanism to increase toxin-mediated virulence during infection.

DOI: https://doi.org/10.1038/s41467-024-53979-8

PLoS Pathog. 2024 Nov 11. 20(11): e1012716

Malnutrition disrupts adaptive immunity during visceral leishmaniasis by enhancing IL-10 production.

Laís Amorim Sacramento, Claudia Gonzalez-Lombana, Phillip Scott.

Protein-energy malnutrition (PEM) is a risk factor for developing visceral leishmaniasis (VL). While nutrient deficiency can impair immunity, its mechanistic impact on protective adaptive immune responses following Leishmania infection remains unknown. To determine the potential negative impacts of malnutrition on anti-parasitic responses in chronic VL, we provided mice with a polynutrient-deficient diet (deficient protein, energy, zinc, and iron) that mimics moderate human malnutrition. The polynutrient-deficient diet resulted in growth stunting and reduced mass of visceral organs and following infection with Leishmania infantum, malnourished-mice harbored more parasites in the spleen and liver. Malnourished and infected mice also had fewer T lymphocytes, with reduced T cell production of IFN-γ required for parasite clearance and enhanced production of the immunosuppressive cytokine, IL-10. To determine if IL-10 was causative in disease progression in the malnourished mice, we treated infected mice with monoclonal antibody α-IL-10R. α-IL-10R treatment reduced the parasite number in malnourished mice, restored the number of T cells producing IFN-γ, and enhanced hepatic granuloma formation. Our results indicate that malnutrition increases VL susceptibility due to defective IFN-γ-mediated immunity attributable to increased IL-10 production.

DOI: https://doi.org/10.1371/journal.ppat.1012716