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1. Diet-induced obesity promotes infection by impairment of the innate antimicrobial defense function of dermal adipocyte progenitors

   https://doi.org/10.1126/scitranslmed.abb5280  

   Zhang, Ling-juan; Guerrero-Juarez, Christian F.; Chen, Stella X.; Zhang, Xiaowei; Yin, Meimei; Li, Fengwu; Wu, Shuai; Chen, Joyce; Li, Min; Liu, Yingzi; et al (January 2021, Science Translational Medicine)

   null (Ed.)

   Infections are a major complication of obesity, but the mechanisms responsible for impaired defense against microbes are not well understood. Here, we found that adipocyte progenitors were lost from the dermis during diet-induced obesity (DIO) in humans and mice. The loss of adipogenic fibroblasts from mice resulted in less antimicrobial peptide production and greatly increased susceptibility to Staphylococcus aureus infection. The decrease in adipocyte progenitors in DIO mice was explained by expression of transforming growth factor–β (TGFβ) by mature adipocytes that then inhibited adipocyte progenitors and the production of cathelicidin in vitro. Administration of a TGFβ receptor inhibitor or a peroxisome proliferator–activated receptor–γ agonist reversed this inhibition in both cultured adipocyte progenitors and in mice and subsequently restored the capacity of obese mice to defend against S. aureus skin infection. Together, these results explain how obesity promotes dysfunction of the antimicrobial function of reactive dermal adipogenesis and identifies potential therapeutic targets to manage skin infection associated with obesity. 

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2. The durability of natural infection and vaccine-induced immunity against future infection by SARS-CoV-2

   Jeffrey P Townsend; Hayley B Hassler; Pratha Sah; Alison P Galvani; Alex Dornburg (July 2022, Proceedings of the National Academy of Sciences of the United States of America)

   The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making. 

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3. Diet- and salinity-induced modifications of the gut microbiota are associated with differential physiological responses to ranavirus infection in Rana sylvatica

   https://doi.org/10.1098/rstb.2022.0121  

   Hughey, Myra C; Warne, Robin; Dulmage, Alexa; Reeve, Robyn E; Curtis, Grace H; Whitfield, Kourtnie; Schock, Danna M; Crespi, Erica (July 2023, Philosophical Transactions of the Royal Society B: Biological Sciences)

   Greater knowledge of how host–microbiome interactions vary with anthropogenic environmental change and influence pathogenic infections is needed to better understand stress-mediated disease outcomes. We investigated how increasing salinization in freshwaters (e.g. due to road de-icing salt runoff) and associated increases in growth of nutritional algae influenced gut bacterial assembly, host physiology and responses to ranavirus exposure in larval wood frogs (Rana sylvatica). Elevating salinity and supplementing a basic larval diet with algae increased larval growth and also increased ranavirus loads. However, larvae given algae did not exhibit elevated kidney corticosterone levels, accelerated development or weight loss post-infection, whereas larvae fed a basic diet did. Thus, algal supplementation reversed a potentially maladaptive stress response to infection observed in prior studies in this system. Algae supplementation also reduced gut bacterial diversity. Notably, we observed higher relative abundances of Firmicutes in treatments with algae—a pattern consistent with increased growth and fat deposition in mammals—that may contribute to the diminished stress responses to infection via regulation of host metabolism and endocrine function. Our study informs mechanistic hypotheses about the role of microbiome mediation of host responses to infection that can be tested in future experiments in this host–pathogen system 

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4. Virus-induced spore formation as a defense mechanism in marine diatoms

   https://doi.org/10.1111/nph.16951  

   Pelusi, A.; De Luca, P.; Manfellotto, F.; Thamatrakoln, K.; Bidle, K.D.; Montresor, M. (February 2021, New phytologist)

   null (Ed.)

   Algal viruses are important contributors to carbon cycling, recycling nutrients and organic material through host lysis. Although viral infection has been described as a primary mechanism of phytoplankton mortality, little is known about host defense responses. We show that viral infection of the bloom-forming, planktonic diatom Chaetoceros socialis induces the mass formation of resting spores, a heavily silicified life cycle stage associated with carbon export due to rapid sinking. Although viral RNA was detected within spores, mature virions were not observed. ‘Infected’ spores were capable of germinating, but did not propagate or transmit infectious viruses. These results demonstrate that diatom spore formation is an effective defense strategy against viral-mediated mortality. They provide a possible mechanistic link between viral infection, bloom termination, and mass carbon export events and highlight an unappreciated role of viruses in regulating diatom life cycle transitions and ecological success. 

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5. Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

   https://doi.org/10.1038/s41598-020-75108-3  

   Rodriguez, Blanca V.; Kuehn, Meta J. (December 2020, Scientific Reports)

   null (Ed.)

   Abstract Bacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such as Staphylococcus aureus and their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells. S. aureus produce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show that S. aureus secretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses. 

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