bims-traimu 2022-11-06 papers

Issue of 2022–11–06
four papers selected by
Yantong Wan, Southern Medical University

J Pediatr (Rio J). 2022 Oct 26. pii: S0021-7557(22)00105-X. [Epub ahead of print]

Implications of the non-specific effect induced by Bacillus Calmette-Guerin (BCG) vaccine on vaccine recommendations.

Ekaterini Goudouris, Carolina Sanchez Aranda, Dirceu Solé.

OBJECTIVES: Since the beginning of its use for the prevention of tuberculosis (TB) in 1921, other uses of BCG (Bacillus Calmette-Guérin) have been proposed, particularly in the treatment of malignant solid tumors, multiple sclerosis, and other autoimmune diseases. Its beneficial impact on other infections, by nontuberculous mycobacteria, and by viruses, has been more often studied in recent years, especially after the introduction of the concept of trained immunity. The present study's objective was to review the possible indications of BCG and the immunological rationale for these indications.
DATA SOURCE: Non-systematic review carried out in the PubMed, SciELO and Google Scholar databases, using the following search terms: "BCG" and "history", "efficacy", "use", "cancer", "trained immunity", "other infections", "autoimmune diseases".
DATA SYNTHESIS: There is epidemiological evidence that BCG can reduce overall child morbidity/mortality beyond what would be expected from TB control. BCG is able to promote cross-immunity with nontuberculous mycobacteria and other bacteria. BCG promotes in vitro changes that increase innate immune response to other infections, mainly viral ones, through mechanisms known as trained immunity. Effects on cancer, except bladder cancer, and on autoimmune and allergic diseases are debatable.
CONCLUSIONS: Despite evidence obtained from in vitro studies, and some epidemiological and clinical evidence, more robust evidence of in vivo efficacy is still needed to justify the use of BCG in clinical practice, in addition to what is recommended by the National Immunization Program for TB prevention and bladder cancer treatment.

Keywords: Autoimmune diseases; BCG; Cancer; Heterologous protection; Trained immunity

DOI: https://doi.org/10.1016/j.jped.2022.09.002

Immunol Rev. 2022 Nov 03.

The emerging role for metabolism in fueling neutrophilic inflammation.

Tyler Morrison, Emily R Watts, Pranvera Sadiku, Sarah R Walmsley.

Neutrophils are a critical element of host defense and are rapidly recruited to inflammatory sites. Such sites are frequently limited in oxygen and/or nutrient availability, presenting a metabolic challenge for infiltrating cells. Long believed to be uniquely dependent on glycolysis, it is now clear that neutrophils possess far greater metabolic plasticity than previously thought, with the capacity to generate energy stores and utilize extracellular proteins to fuel central carbon metabolism and biosynthetic activity. Out-with cellular energetics, metabolic programs have also been implicated in the production of neutrophils and their progenitors in the bone marrow compartment, activation of neutrophil antimicrobial responses, inflammatory and cell survival signaling cascades, and training of the innate immune response. Thus, understanding the mechanisms by which metabolic processes sustain changes in neutrophil effector functions and how these are subverted in disease states provides exciting new avenues for the treatment of dysfunctional neutrophilic inflammation which are lacking in clinical practice to date.

Keywords: immunometabolism; inflammation; neutrophil; trained immunity

DOI: https://doi.org/10.1111/imr.13157

Immunity. 2022 Oct 24. pii: S1074-7613(22)00558-1. [Epub ahead of print]

Sterilizing immunity: Understanding COVID-19.

Ilka Wahl, Hedda Wardemann.

Immune memory develops during primary infections to protect from future exposures to the same pathogen. Vaccines mimic this response and induce immune memory that protects from severe disease and, in some cases, from symptomatic infection. If the pathogen is eliminated before it can replicate, natural and vaccine-induced immune memory can prevent the establishment of the infection, mediating sterilizing immunity. Sterilizing immunity protects the individual and prevents transmission to new hosts, thereby contributing to protection at a population level. Here, we describe the basic concepts of sterilizing immunity and discuss its relevance for protection in the context of SARS-CoV-2.

DOI: https://doi.org/10.1016/j.immuni.2022.10.017

PLoS Pathog. 2022 10;18(10): e1010897

An innate ability: How do basal invertebrates manage their chronic exposure to microbes?

Leah M Williams, Thomas D Gilmore.

Homologs of mammalian innate immune sensing and downstream pathway proteins have been discovered in a variety of basal invertebrates, including cnidarians and sponges, as well as some single-celled protists. Although the structures of these proteins vary among the basal organisms, many of the activities found in their mammalian counterparts are conserved. This is especially true for the Toll-like receptor (TLR) and cGAS-STING pathways that lead to downstream activation of transcription factor NF-κB. In this short perspective, we describe the evidence that TLR and cGAS-STING signaling to NF-κB is also involved in immunity in basal animals, as well as in the maintenance of microbial symbionts. Different from terrestrial animals, immunity in many marine invertebrates might have a constitutively active state (to protect against continual exposure to resident or waterborne microbes), as well as a hyperactive state that can be induced by pathogens at both transcriptional and posttranscriptional levels. Research on basal immunity may be important for (1) understanding different approaches that organisms take to sensing and protecting against microbes, as well as in maintaining microbial symbionts; (2) the identification of novel antimicrobial effector genes and processes; and (3) the molecular pathways that are being altered in basal marine invertebrates in the face of the effects of a changing environment.

DOI: https://doi.org/10.1371/journal.ppat.1010897