The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL1505

Clua, Patricia; Tomokiyo, Mikado; Tonetti, Fernanda Raya; Islam, M. S.; Castillo, Valeria García; Marcial, Guillermo; Salva, Susana; Alvarez, Susana; Takahashi, Hideki; Kurata, Shoichiro; Kitazawa, Haruki; Villena, Julio

doi:10.3390/cells9071653

Cited by 22 publications

(42 citation statements)

References 65 publications

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“…Beyond the poly I:C class of TLR3-stimulating molecules, oral administration of purified L. rhamnosus CRL1505 peptidoglycan confers resistance to RSV infection associated with decreased viral loads in the lungs and augmented cytokine responses ( 127 ). Protection against RSV and subsequent secondary infection to pneumococcal pneumonia was found to be dependent on TLR3 ( 128 , 130 ) and macrophages ( 173 ). In an immunocompromised-malnourished model, it was found that immunostimulatory properties of CRL1505 peptidoglycan extended beyond augmentation of innate immunity.…”

Section: Toll-like Receptor Agonist-mediated Trained Immunity and Promentioning

confidence: 99%

TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection

et al. 2021

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Despite advances in critical care medicine, infection remains a significant problem that continues to be complicated with the challenge of antibiotic resistance. Immunocompromised patients are highly susceptible to development of severe infection which often progresses to the life-threatening condition of sepsis. Thus, immunotherapies aimed at boosting host immune defenses are highly attractive strategies to ward off infection and protect patients. Recently there has been mounting evidence that activation of the innate immune system can confer long-term functional reprogramming whereby innate leukocytes mount more robust responses upon secondary exposure to a pathogen for more efficient clearance and host protection, termed trained immunity. Toll-like receptor (TLR) agonists are a class of agents which have been shown to trigger the phenomenon of trained immunity through metabolic reprogramming and epigenetic modifications which drive profound augmentation of antimicrobial functions. Immunomodulatory TLR agonists are also highly beneficial as vaccine adjuvants. This review provides an overview on TLR signaling and our current understanding of TLR agonists which show promise as immunotherapeutic agents for combating infection. A brief discussion on our current understanding of underlying mechanisms is also provided. Although an evolving field, TLR agonists hold strong therapeutic potential as immunomodulators and merit further investigation for clinical translation.

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Section: Toll-like Receptor Agonist-mediated Trained Immunity and Promentioning

confidence: 99%

TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection

et al. 2021

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“…The albumin content in BAL was quantified as an indicator of the increased permeability of the bronchoalveolar capillary barrier [ 21 ]. In addition, lactate dehydrogenase (LDH) activity was quantified as an indicator of general cytotoxicity [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

et al. 2021

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Previously, we demonstrated that the nasal administration of Dolosigranulum pigrum 040417 differentially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 2 in infant mice. In this work, we aimed to evaluate the beneficial effects of D. pigrum 040417 in the context of Streptococcus pneumoniae infection and characterize the role of alveolar macrophages (AMs) in the immunomodulatory properties of this respiratory commensal bacterium. The nasal administration of D. pigrum 040417 to infant mice significantly increased their resistance to pneumococcal infection, differentially modulated respiratory cytokines production, and reduced lung injuries. These effects were associated to the ability of the 040417 strain to modulate AMs function. Depletion of AMs significantly reduced the capacity of the 040417 strain to improve both the reduction of pathogen loads and the protection against lung tissue damage. We also demonstrated that the immunomodulatory properties of D. pigrum are strain-specific, as D. pigrum 030918 was not able to modulate respiratory immunity or to increase the resistance of mice to an S. pneumoniae infection. These findings enhanced our knowledge regarding the immunological mechanisms involved in modulation of respiratory immunity induced by beneficial respiratory commensal bacteria and suggested that particular strains could be used as next-generation probiotics.

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“…While the exact MAMPs responsible for the probiotic antiviral effects in the airways are not yet well-defined (see Outstanding Questions), an interesting observation was that live and heat-killed Lacticaseibacillus rhamnosus GG were equally protective against influenza when administered intranasally [60], suggesting heat-stable, non-proteinaceous cellular components as candidate MAMPs. Similarly, for the related strain L. rhamnosus CRL1505 and the respiratory commensal Dolosigranulum pigrum 040417, both the live cells and their cell components (purified peptidoglycan and isolated cell wall) were protective against RSV infection and secondary pneumococcal pneumonia in mice through stimulated production of IFN-γ, IL-10, and IFN-β in the airways [21]. In contrast, the isolated peptidoglycan of Limosilactobacillus reuteri F275 was insufficient to protect mice from pneumonia virus, despite stimulating neutrophil influx and increasing proinflammatory cytokine production in the airways [64].…”

Section: Bacterial Stimulation Of Innate Immunity Demonstrated In Vivomentioning

confidence: 99%

“…Respiratory viral infection is a complex process that begins with virion attachment to host cells and endocytosis, followed by replication inside the host cell, assembly, and release of novel viral particles that initiate further infection (Figure 1) [12,[20][21][22][23][24][25].…”

Section: Bacterial Inhibition Of Viral Entry and Infectivitymentioning

confidence: 99%

“…The bacterial superinfections in SARS-CoV-2 and influenza patients are predominantly caused by the opportunistic pathogens Mycoplasma pneumoniae, Pseudomonas aeruginosa, H. influenzae, S. pneumoniae, and K. pneumoniae [15,89]. Preventive intranasal administration of beneficial bacteria in vivo can ameliorate S. pneumoniae superinfection through immunomodulatory mechanisms (Table 1) [8,21]. Recently, we also demonstrated direct in vitro inhibitory action of the L. casei AMBR2 URT isolate against opportunistic pathogens H. influenzae and S. aureus [5].…”

Section: Beneficial Bacteria Inhibit Bacterial Pathogens Associated With Viral Diseasementioning

confidence: 99%

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Topical Microbial Therapeutics against Respiratory Viral Infections

Spacova

Boeck

Bron

et al. 2021

Trends in Molecular Medicine

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Emerging evidence suggests that microbial therapeutics can prevent and treat respiratory viral diseases, especially when applied directly to the airways. This review presents established beneficial effects of locally administered microbial therapeutics against respiratory viral diseases and the inferred related molecular mechanisms. Several mechanisms established in the intestinal probiotics field as well as novel, niche-specific insights are relevant in the airways. Studies at cellular and organism levels highlight biologically plausible but strain-specific and host and virus context-dependent mechanisms, underlying the potential of beneficial bacteria. Large-scale clinical studies can now be rationally designed to provide a bench-to-bedside translation of the multifactorial bacterial mechanisms within the host respiratory tract, to diminish the incidence and severity of viral infections and the concomitant complications. The Respiratory Microbiota and Viral InfectionsThe human airways represent an important ecological habitat consisting of the upper respiratory tract (URT) (the nose, paranasal sinuses, nasopharynx, and larynx above the vocal cords) and the lower respiratory tract (LRT) (the larynx below the vocal cords, tracheobronchial tree containing the trachea, bronchi, and bronchioles, and the alveoli) [1]. The airways, like the gut, host diverse communities of microorganisms, collectively forming the microbiota (see Glossary), that undergo continuous interactions with each other, the host, and exogenous microbes [1-3]. There are, however, notable differences between the gut and respiratory tract, including significantly lower microbial biomass and biodiversity in the airways and specific epithelial and immune cell types and mucus composition that impact the microbe-host interactions [1,3].The microbiota of the URT and LRT of healthy individuals are a continuum of taxa shared due to processes such as mucosal dispersion and micro-aspiration from the URT to the LRT [1,2]. As has been well-established in the gastrointestinal tract, emerging evidence suggests that endogenous microbial communities also play a pivotal role in airway health through preventing colonization by pathogens and maintaining immune homeostasis [1]. An increasing number of microbiome studies indicate that a healthy URT microbiota includes taxa such as Corynebacterium, Staphylococcus, Streptococcus, Fusobacterium, Moraxella, Prevotella, Rothia, and lactic acid bacteria (e.g., Lactobacillaceae and Dolosigranulum) [4-6]. It is not yet clear which of these taxa are key for maintaining respiratory health. Based on current evidence, Lactobacillaceae [5], Rothia [7], and Dolosigranulum [5,8] are generally associated with health, while the opportunistic pathogens Streptococcus pneumoniae, Haemophilus influenzae, and potentially Moraxella catarrhalis are linked with excessive inflammation and respiratory infection [2,9]. Respiratory tract infections are among the leading global causes of death [10]. Most acute URT infections and cases of bronchiti...

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The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL1505

Cited by 22 publications

References 65 publications

TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection

TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection

The Respiratory Commensal Bacterium Dolosigranulum pigrum 040417 Improves the Innate Immune Response to Streptococcus pneumoniae

Topical Microbial Therapeutics against Respiratory Viral Infections

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