bims-bac4me 2023-03-05 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2023–03–05
twelve papers selected by
Chun-Chi Chang, Universitäts Spital Zürich

Trained Immunity in Allergic Asthma.
A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice.
Role of the skin microbiota and intestinal microbiome in rosacea.
Role of mitochondria in regulating immune response during bacterial infection.
IL-27 inhibits anti- Mycobacterium tuberculosis innate immune activity of primary human macrophages.
Immunity to fungi in the lung.
Cross-Protection against Acute Staphylococcus aureus Lung Infection in Mice by a D-Glutamate Auxotrophic Vaccine Candidate.
Modulation by luminal factors on the functions and migration of intestinal innate immunity.
Ready, STAT3, Go! Bacteria in the race for M2 macrophage polarisation.
Skin Barrier Immunology from early life to adulthood.
CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis.
Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

J Allergy Clin Immunol. 2023 Mar 01. pii: S0091-6749(23)00283-X. [Epub ahead of print]

Trained Immunity in Allergic Asthma.

Michael Wegmann.



Keywords:  asthma; epigenetic; hygiene hypothesis; infection; innate immunity; trained immunity

DOI:  https://doi.org/10.1016/j.jaci.2023.02.023
J Nanobiotechnology. 2023 Mar 02. 21(1): 74

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice.

Duo Li, Weiran Li, Peng Zheng, Ying Yang, Qingwen Liu, Yongmao Hu, Jinrong He, Qiong Long, Yanbing Ma.

  Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, β-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1β, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of β-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.

Keywords:  MDP; Nanovaccine; Trained immunity; Tumor; β-glucan

DOI:  https://doi.org/10.1186/s12951-023-01832-3
Front Microbiol. 2023 ;14 1108661

Role of the skin microbiota and intestinal microbiome in rosacea.

Weitao Zhu, Michael R Hamblin, Xiang Wen.

  Rosacea is a chronic inflammatory cutaneous disorder of uncertain etiology that mainly affects the centrofacial region, including cheeks, nose, chin, forehead, and eyes. The pathogenesis of rosacea remains unclear because it involves several complex factors. Additionally, the potential treatment methods need to be explored. We reviewed the common bacterial species in the skin microbiota and gut microbiota of rosacea patients such as Demodex folliculorum, Staphylococcus epidermidis, Bacillus oleronius, Cutibacterium acnes, and Helicobacter pylori and identified their role in the pathogenesis. Besides, we summarized the influence factors such as temperature and age on rosacea patients. We also systematically reviewed the commonly used clinical treatment methods, including antibiotics, probiotics. as well as their treatment mechanism and application precautions.

Keywords:  gastrointestinal microbiome; influence factors; rosacea; skin microbiota; treatment

DOI:  https://doi.org/10.3389/fmicb.2023.1108661
Int Rev Cell Mol Biol. 2023 ;pii: S1937-6448(22)00138-1. [Epub ahead of print]374 159-200

Role of mitochondria in regulating immune response during bacterial infection.

Shaziya Khan, Swarnali Basu, Desh Raj, Amit Lahiri.

  Mitochondria are dynamic organelles of eukaryotes involved in energy production and fatty acid oxidation. Besides maintaining ATP production, calcium signaling, cellular apoptosis, and fatty acid synthesis, mitochondria are also known as the central hub of the immune system as it regulates the innate immune pathway during infection. Mitochondria mediated immune functions mainly involve regulation of reactive oxygen species production, inflammasome activation, cytokine secretion, and apoptosis of infected cells. Recent findings indicate that cellular mitochondria undergo constant biogenesis, fission, fusion and degradation, and these dynamics regulate cellular immuno-metabolism. Several intracellular pathogens target and modulate these normal functions of mitochondria to facilitate their own survival and growth. De-regulation of mitochondrial functions and dynamics favors bacterial infection and pathogens are able to protect themselves from mitochondria mediated immune responses. Here, we will discuss how mitochondria mediated anti-bacterial immune pathways help the host to evade pathogenic insult. In addition, examples of bacterial pathogens modulating mitochondrial metabolism and dynamics will also be elaborated. Study of these interactions between the mitochondria and bacterial pathogens during infection will lead to a better understanding of the mitochondrial metabolism pathways and dynamics important for the establishment of bacterial diseases. In conclusion, detailed studies on how mitochondria regulate the immune response during bacterial infection can open up new avenues to develop mitochondria centric anti-bacterial therapeutics.

Keywords:  Apoptosis; Bacteria; Immune response; Mitochondria; Mitochondrial dynamics

DOI:  https://doi.org/10.1016/bs.ircmb.2022.10.004
Tuberculosis (Edinb). 2023 Feb 24. pii: S1472-9792(23)00024-0. [Epub ahead of print]139 102326

IL-27 inhibits anti- Mycobacterium tuberculosis innate immune activity of primary human macrophages.

Hailey Gollnick, Jamie Barber, Robert J Wilkinson, Sandra Newton, Ankita Garg.

  Mycobacterium tuberculosis (M. tuberculosis) is an intracellular pathogen that primarily infects macrophages. Despite a robust anti-mycobacterial response, many times macrophages are unable to control M. tuberculosis. The purpose of this study was to investigate the mechanism by which the immunoregulatory cytokine IL-27 inhibits the anti-mycobacterial activity of primary human macrophages. We found concerted production of IL-27 and anti-mycobacterial cytokines by M. tuberculosis-infected macrophages in a toll-like receptor (TLR) dependent manner. Notably, IL-27 suppressed the production of anti-mycobacterial cytokines TNFα, IL-6, IL-1β, and IL-15 by M. tuberculosis-infected macrophages. IL-27 limits the anti-mycobacterial activity of macrophages by reducing Cyp27B, cathelicidin (LL-37), LC3B lipidation, and increasing IL-10 production. Furthermore, neutralizing both IL-27 and IL-10 increased the expression of proteins involved in LC3-associated phagocytosis (LAP) pathway for bacterial clearance, namely vacuolar-ATPase, NOX2, and RUN-domain containing protein RUBCN. These results implicate IL-27 is a prominent cytokine that impedes M. tuberculosis clearance.

Keywords:  Human macrophages(3), innate immunity(4), cytokines(5); IL-27(1); M. tuberculosis(2)

DOI:  https://doi.org/10.1016/j.tube.2023.102326
Semin Immunol. 2023 Feb 24. pii: S1044-5323(23)00019-2. [Epub ahead of print]66 101728

Immunity to fungi in the lung.

Lena J Heung, Darin L Wiesner, Keyi Wang, Amariliz Rivera, Tobias M Hohl.

  The respiratory tree maintains sterilizing immunity against human fungal pathogens. Humans inhale ubiquitous filamentous molds and geographically restricted dimorphic fungal pathogens that form small airborne conidia. In addition, pathogenic yeasts, exemplified by encapsulated Cryptococcus species, and Pneumocystis pose significant fungal threats to the lung. Classically, fungal pneumonia occurs in immune compromised individuals, specifically in patients with HIV/AIDS, in patients with hematologic malignancies, in organ transplant recipients, and in patients treated with corticosteroids and targeted biologics that impair fungal immune surveillance in the lung. The emergence of fungal co-infections during severe influenza and COVID-19 underscores the impairment of fungus-specific host defense pathways in the lung by respiratory viruses and by medical therapies to treat viral infections. Beyond life-threatening invasive syndromes, fungal antigen exposure can exacerbate allergenic disease in the lung. In this review, we discuss emerging principles of lung-specific antifungal immunity, integrate the contributions and cooperation of lung epithelial, innate immune, and adaptive immune cells to mucosal barrier immunity, and highlight the pathogenesis of fungal-associated allergenic disease. Improved understanding of fungus-specific immunity in the respiratory tree has paved the way to develop improved diagnostic, pre-emptive, therapeutic, and vaccine approaches for fungal diseases of the lung.

Keywords:  Aspergillus; Blastomyces; Cryptococcus; Fungus; Histoplasma; Immunity; Infection; Innate; Lung; Lymphocyte; Macrophage; Monocyte; Mucomycosis; Mucorales; Mycosis; Neutrophil; Paracoccidioides; Pneumonia; T cell; Talaromyces

DOI:  https://doi.org/10.1016/j.smim.2023.101728
Vaccines (Basel). 2023 Jan 17. pii: 210. [Epub ahead of print]11(2):

Cross-Protection against Acute Staphylococcus aureus Lung Infection in Mice by a D-Glutamate Auxotrophic Vaccine Candidate.

Patricia García, Maria P Cabral, Alejandro Beceiro, Miriam Moscoso, Germán Bou.

  Staphylococcus aureus is regarded as a threatening bacterial pathogen causing invasive pneumonia in healthcare settings and in the community. The continuous emergence of multidrug resistant strains is narrowing the treatment options for these infections. The development of an effective S. aureus vaccine is, therefore, a global priority. We have previously developed a vaccine candidate, 132 ΔmurI Δdat, which is auxotrophic for D-glutamate, and protects against sepsis caused by S. aureus. In the present study, we explored the potential of this vaccine candidate to prevent staphylococcal pneumonia, by using an acute lung infection model in BALB/c mice. Intranasal inoculation of the vaccine strain yielded transitory colonization of the lung tissue, stimulated production of relevant serum IgG and secretory IgA antibodies in the lung and distal vaginal mucosa and conferred cross-protection to acute pneumonia caused by clinically important S. aureus strains. Although these findings are promising, additional research is needed to minimize dose-dependent toxicity for safer intranasal immunization with this vaccine candidate.

Keywords:  D-amino acid transaminase gene; Staphylococcus aureus; acute lung infection model; auxotrophic; glutamate racemase gene; intranasal immunization; live-attenuated vaccine

DOI:  https://doi.org/10.3390/vaccines11020210
Front Immunol. 2023 ;14 1113467

Modulation by luminal factors on the functions and migration of intestinal innate immunity.

Masaaki Higashiyama, Soichiro Miura, Ryota Hokari.

  Luminal antigens, nutrients, metabolites from commensal bacteria, bile acids, or neuropeptides influence the function and trafficking of immune cells in the intestine. Among the immune cells in the gut, innate lymphoid cells, including macrophages, neutrophils, dendritic cells, mast cells, and innate lymphoid cells, play an important role for the maintenance of intestinal homeostasis through a rapid immune response to luminal pathogens. These innate cells are influenced by several luminal factors, possibly leading to dysregulated gut immunity and intestinal disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and intestinal allergy. Luminal factors are sensed by distinct neuro-immune cell units, which also have a strong impact on immunoregulation of the gut. Immune cell trafficking from the blood stream through the lymphatic organ to lymphatics, an essential function for immune responses, is also modulated by luminal factors. This mini-review examines knowledge of luminal and neural factors that regulate and modulate response and migration of leukocytes including innate immune cells, some of which are clinically associated with pathological intestinal inflammation.

Keywords:  gut immunity; inflammatory bowel disease; innate immunity; intestinal allergy; leukocytes; luminal factors; migration; neuropeptides

DOI:  https://doi.org/10.3389/fimmu.2023.1113467
Curr Opin Microbiol. 2023 Feb 27. pii: S1369-5274(23)00022-X. [Epub ahead of print]73 102285

Ready, STAT3, Go! Bacteria in the race for M2 macrophage polarisation.

Ioanna Panagi, Teresa Lm Thurston.

Despite macrophages representing professional immune cells that are integral to the host defences against microbial threats, several intracellular bacteria not only infect, but survive, replicate and often persist in these cells. This is perhaps possible because not all macrophages are the same. Instead, macrophages are loosely divided into two classes: the M1 'classically activated' pro-inflammatory subset and the M2 'alternatively activated' cells that are generally anti-inflammatory and infection-permissive. In this review, we summarise recent findings explaining how several intracellular pathogens, often using secreted effectors, rewire host circuitry in favour of an anti-inflammatory niche. A common theme is the phosphorylation and activation of the signal transducer and activator of transcription-3 (STAT3) transcription factor. We describe and compare the diverse mechanisms employed and reflect how such non-canonical processes may have evolved to circumvent regulation by the host, providing a potent means by which different pathogens manipulate the cells they infect.

DOI: https://doi.org/10.1016/j.mib.2023.102285
Mucosal Immunol. 2023 Mar 01. pii: S1933-0219(23)00013-2. [Epub ahead of print]

Skin Barrier Immunology from early life to adulthood.

Aurélien Trompette, Niki D Ubags.

  Our skin has a unique barrier function which is imperative for the body's protection against external pathogens and environmental insults. While interacting closely and sharing many similarities with key mucosal barrier sites, such as the gut and the lung, the skin also provides protection for internal tissues and organs and has a distinct lipid and chemical composition. Skin immunity develops over time and is influenced by a multiplicity of different factors, including lifestyle, genetics, and environmental exposures. Alterations in early life skin immune and structural development may have long-term consequences for skin health. In this review we summarize the current knowledge on cutaneous barrier and immune development from early life to adulthood with an overview of skin physiology and immune responses. We specifically highlight the influence of the skin microenvironment and other host intrinsic, host extrinsic (e.g. skin microbiome), and environmental factors on early life cutaneous immunity.

Keywords:  barrier immunology; early life; skin development

DOI:  https://doi.org/10.1016/j.mucimm.2023.02.005
Cell Rep. 2023 Mar 01. pii: S2211-1247(23)00182-1. [Epub ahead of print]42(3): 112171

CD169+ macrophage intrinsic IL-10 production regulates immune homeostasis during sepsis.

Stephen T Yeung, Luis J Ovando, Ashley J Russo, Vijay A Rathinam, Kamal M Khanna.

  Macrophages facilitate critical functions in regulating pathogen clearance and immune homeostasis in tissues. The remarkable functional diversity exhibited by macrophage subsets is dependent on tissue environment and the nature of the pathological insult. Our current knowledge of the mechanisms that regulate the multifaceted counter-inflammatory responses mediated by macrophages remains incomplete. Here, we report that CD169+ macrophage subsets are necessary for protection under excessive inflammatory conditions. We show that in the absence of these macrophages, even under mild septic conditions, mice fail to survive and exhibit increased production of inflammatory cytokines. Mechanistically, CD169+ macrophages control inflammatory responses via interleukin-10 (IL-10), as CD169+ macrophage-specific deletion of IL-10 was lethal during septic conditions, and recombinant IL-10 treatment reduced lipopolysaccharide (LPS)-induced lethality in mice lacking CD169+ macrophages. Collectively, our findings show a pivotal homeostatic role for CD169+ macrophages and suggest they may serve as an important target for therapy under damaging inflammatory conditions.

Keywords:  CD169; CP: Immunology; G-CSF; IL-10; LPS; Siglec-1; macrophages; septic shock

DOI:  https://doi.org/10.1016/j.celrep.2023.112171
bioRxiv. 2023 Feb 23. pii: 2023.02.23.529713. [Epub ahead of print]

Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

Edward J A Douglas, Nathanael Palk, Tarcisio Brignoli, Dina Altwiley, Marcia Boura, Maisem Laabei, Mario Recker, Gordon Y C Cheung, Ryan Liu, Roger C Hsieh, Michael Otto, Eoin Oâ Brien, Rachel M McLoughlin, Ruth C Massey.

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA , was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of this protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

DOI: https://doi.org/10.1101/2023.02.23.529713