bims-traimu 2023-02-05 papers

Issue of 2023–02–05
seven papers selected by
Yantong Wan, Southern Medical University

Front Immunol. 2022 ;13 984859

Weight cycling induces innate immune memory in adipose tissue macrophages.

Heather L Caslin, Matthew A Cottam, Jacqueline M Piñon, Likem Y Boney, Alyssa H Hasty.

Introduction: Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease. We previously reported that male mice retain obesity-associated immunological changes even after weight loss, suggesting that immune cells may remember the state of obesity. Therefore, we hypothesized that cycles of weight gain and loss, otherwise known as weight cycling, can induce innate memory in adipose macrophages.
Methods: Bone marrow derived macrophages were primed with palmitic acid or adipose tissue conditioned media in a culture model of innate immune memory. Mice also put on low fat or high fat diets over 14-27 weeks to induce weight gain, weight loss, and weight cycling.
Results: Priming cells with palmitic acid or adipose tissue conditioned media from obese mice increased maximal glycolysis and oxidative phosphorylation and increased LPS-induced TNFα and IL-6 production. Palmitic acid effects were dependent on TLR4 and impaired by methyltransferase inhibition and AMPK activation. While weight loss improved glucose tolerance in mice, adipose macrophages were primed for greater activation to subsequent stimulation by LPS ex vivo as measured by cytokine production. In the model of weight cycling, adipose macrophages had elevated metabolism and secreted higher levels of basal TNFα, suggesting that weight loss can also prime macrophages for heighted activation to weight regain.
Discussion: Together, these data suggest that weight loss following obesity can prime adipose macrophages for enhanced inflammation upon weight regain. This innate immune memory response may contribute to worsened glucose tolerance following weight cycling.

Keywords: adipose tissue macrophages; innate immune memory; obesity; trained innate immunity; weight cycling; weight loss

DOI: https://doi.org/10.3389/fimmu.2022.984859

Trends Immunol. 2023 Jan 11. pii: S1471-4906(23)00005-4. [Epub ahead of print]

COVID-19 vaccines and a perspective on Africa.

Alberto Mantovani, Maria Rescigno, Guido Forni, Francesca Tognon, Giovanni Putoto, Jerry Ictho, Peter Lochoro.

Vaccines have dramatically changed the COVID-19 pandemic. Over 30 vaccines that were developed on four main platforms are currently being used globally, but a deep dissection of the immunological mechanisms by which they operate is limited to only a few of them. Here, we review the evidence describing specific aspects of the modes of action of COVID-19 vaccines; these include innate immunity, trained innate immunity, and mucosal responses. We also discuss the use of COVID-19 vaccines in the African continent which is ridden with inequality in its access to vaccines and vaccine-related immunological research. We argue that strengthening immunology research in Africa should inform on fundamental aspects of vaccination, including the relevance of genetics, trained innate immunity, and microbiome diversity.

Keywords: Africa; COVID-19; immune imprinting; innate immunity; long COVID; mucosal responses; trained immunity; vaccine inequality; vaccines

DOI: https://doi.org/10.1016/j.it.2023.01.005

J Allergy Clin Immunol. 2023 Jan 28. pii: S0091-6749(23)00138-0. [Epub ahead of print]

Interactions Between Host Epigenetics and Microbiota: Who Does What to Whom, When and Why?

Donata Vercelli, Susan V Lynch.

Keywords: DNA methylation; childhood asthma; maternal immunity; microbiome; trained immunity

DOI: https://doi.org/10.1016/j.jaci.2023.01.018

bioRxiv. 2023 Jan 19. pii: 2023.01.16.524322. [Epub ahead of print]

3D Chromatin Dynamics during Innate and Adaptive Immune Memory Acquisition.

Endi K Santosa, Colleen M Lau, Merve Sahin, Christina S Leslie, Joseph C Sun.

Immune cells responding to pathogens undergo molecular changes that are intimately linked to genome organization. Recent work has demonstrated that natural killer (NK) and CD8 + T cells experience substantial transcriptomic and epigenetic rewiring during their differentiation from na√Øve to effector to memory cells. Whether these molecular adaptations are accompanied by changes in three-dimensional (3D) chromatin architecture is unknown. In this study, we combine histone profiling, ATAC-seq, RNA-seq and high-throughput chromatin capture (HiC) assay to investigate the dynamics of one-dimensional (1D) and 3D chromatin during the differentiation of innate and adaptive lymphocytes. To this end, we discovered a coordinated 1D and 3D epigenetic remodeling during innate immune memory differentiation, and demonstrate that effector CD8 + T cells adopt an NK-like architectural program that is maintained in memory cells. Altogether, our study reveals the dynamic nature of the 1D and 3D genome during the formation of innate and adaptive immunological memory.

DOI: https://doi.org/10.1101/2023.01.16.524322

Front Immunol. 2022 ;13 1085786

Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques.

Edith M Walker, Kristen M Merino, Nadia Slisarenko, Brooke F Grasperge, Smriti Mehra, Chad J Roy, Deepak Kaushal, Namita Rout.

Background: Although BCG vaccine protects infants from tuberculosis (TB), it has limited efficacy in adults against pulmonary TB. Further, HIV coinfection significantly increases the risk of developing active TB. In the lack of defined correlates of protection in TB disease, it is essential to explore immune responses beyond conventional CD4 T cells to gain a better understanding of the mechanisms of TB immunity.
Methods: Here, we evaluated unconventional lipid-reactive T cell responses in cynomolgus macaques following aerosol BCG inoculation and examined the impact of subsequent SIV infection on these responses. Immune responses to cellular lipids of M. bovis and M. tuberculosis were examined ex vivo in peripheral blood and bronchioalveolar lavage (BAL).
Results: Prior to BCG inoculation, innate-like IFN-γ responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL γδT cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-γ responses to mycobacterial lipids in peripheral blood and BAL, suggesting the induction of systemic and local Th1-type response in lipid-reactive T cells. Subsequent SIV infection resulted in a significant loss of IL-7R expression on blood and BAL γδT cells. Additionally, IFN-γ responses of mycobacterial lipid-reactive T cells in BAL fluid were significantly lower in SIV-infected macaques, while perforin production was maintained through chronic SIV infection.
Conclusions: Overall, these data suggest that despite SIV-induced decline in IL-7R expression and IFN-γ production by mycobacterial lipid-reactive T cells, their cytolytic potential is maintained. A deeper understanding of anti-mycobacterial lipid-reactive T cell functions may inform novel approaches to enhance TB control in individuals with or without HIV infection.

Keywords: BCG; SIV; lipid antigen; macaque; tuberculosis; γδT

DOI: https://doi.org/10.3389/fimmu.2022.1085786

Clin Microbiol Infect. 2023 Jan 31. pii: S1198-743X(23)00044-7. [Epub ahead of print]

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial.

writing committee for the BCG-PRIME study group

OBJECTIVES: To test whether BCG vaccination would reduce the incidence of COVID-19 and other respiratory tract infections in older adults with one or more comorbidities.
METHODS: Community-dwelling adults over 60 years old with one or more underlying comorbidities and no contra-indications for BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for six months. The primary endpoint was self-reported test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTI (i.e. RTI including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine and Gray regression, accounting for competing events.
RESULTS: A total of 6,112 participants with a median age of 69 years (inter-quartile range 65-74) and median of 2 (inter-quartile range 1-3) comorbidities were randomized to BCG (n=3,058) or placebo (n=3,054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients (hazard ratio (HR) 1.12; 95% confidence interval (CI) 0.87-1.44). COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR 0.86; 95% CI 0.46-1.61). During the study period 13 BCG recipients compared to 18 placebo recipients died (HR 0.71; 95% CI 0.35 - 1.43) of which 11 deaths (35%) were COVID-19 related six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR 0.92; 95% CI 0.66-1.28).
CONCLUSION: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization or clinically relevant RTI.

DOI: https://doi.org/10.1016/j.cmi.2023.01.019