Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studies

Troy, Niamh M.; Strickland, Deborah; Serralha, Michael; Jong, Emma de; Jones, Anya C.; Read, James F.; Galbraith, Sally; Islam, Zahir; Kaur, Parwinder; Mincham, Kyle T; Holt, Barbara J.; Sly, Peter D.; Bosco, Anthony; Holt, Patrick G.

doi:10.1016/j.jaci.2022.01.001

Cited by 15 publications

(17 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most TLRs have been reported to use an adaptor molecule, the protein product of MyD88, the absence of which alters TLR4 downstream signaling [6]. When the TLR pathway is activated, nuclear factor kappa-B (NF-kB) is subsequently activated and translocated to the nucleus to induce various inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) [7]. Although these proinflammatory cytokines continue to mediate inflammation and exacerbate kidney disease, Foods 2022, 11, 3042 2 of 13 hypoglycemic and lipid-lowering drugs may help inhibit the progression of nephritis [8].…”

Section: Introductionmentioning

confidence: 99%

Lycopene-Loaded Bilosomes Ameliorate High-Fat Diet-Induced Chronic Nephritis in Mice through the TLR4/MyD88 Inflammatory Pathway

Liu

Wang

et al. 2022

Foods

View full text Add to dashboard Cite

Chronic kidney disease caused by a high-fat diet (HFD)-induced metabolic syndrome has received widespread attention. Lycopene has a wide range of biological activities and can improve a variety of chronic diseases through anti-inflammatory effects. In this study, HFD-fed mice were used as a metabolic syndrome model to evaluate the protective effect of lycopene in a sustained-release vehicle (bilosomes) in the small intestine against renal injury and to determine whether the TLR4/MyD88 pathway and related metabolic pathways are involved in this process. The results showed that lycopene bilosomes alleviated HFD-induced kidney damage, as evidenced by lower serum urea nitrogen, creatinine, and uric acid levels. Histopathology studies showed that lycopene bilosomes attenuated HFD-induced tubular cell and glomerular injury. In addition, Elisa, RT-PCR, and Western blotting results showed that lycopene bilosomes also reduced the expression of inflammatory factors such as TLR4, MyD88, NF-kB, TNF-a, and IL-6 in mouse kidneys. The mechanism was to attenuate renal inflammatory response by inhibiting the TLR4/MyD88 inflammatory pathway. These findings suggested that lycopene can alleviate nephritis and metabolic disorders caused by HFD, inhibiting the TLR4/MyD88 inflammatory pathway and its downstream pro-inflammatory cytokines and further regulating the vitamin K metabolism, beta-alanine metabolism, and glutathione metabolism pathways to relieve chronic nephritis.

show abstract

Section: Introductionmentioning

confidence: 99%

Lycopene-Loaded Bilosomes Ameliorate High-Fat Diet-Induced Chronic Nephritis in Mice through the TLR4/MyD88 Inflammatory Pathway

Liu

Wang

et al. 2022

Foods

View full text Add to dashboard Cite

show abstract

“…The underlying mechanisms for the potential immune training-based effects leading to protection against severe lower respiratory tract infections, are only partially understood. However, interesting new data came from a recent placebo-controlled trial in infants, showing that the OM-85-induced reduction in respiratory infection frequency and/or duration, was associated with immune changes indicative of innate immune training ( 76 ). Similar changes and effects have been described in the animal model studies included in the present review ( 39 , 62 ).…”

Section: Discussionmentioning

confidence: 99%

“…Similar changes and effects have been described in the animal model studies included in the present review ( 39 , 62 ). In the study by Troy and colleagues, human peripheral blood mononuclear cells obtained from infants, were exposed ex-vivo to OM-85 (or placebo) and then stimulated with the bacteria mimicking lipopolysaccharide (LPS) ( Figure 4 ) ( 76 ). In cultures exposed to OM-85, upregulation of IFN signaling, was accompanied by, (i) network rewiring resulting in increased coordination of TLR4 expression with IFN pathway–associated genes (especially master regulator IRF7); ii) segregation of TNF and IFN- γ (which potentially synergize to exaggerate inflammatory sequelae) into separate expression modules; iii) reduced size/complexity of the main proinflammatory network module, containing, IL-1, IL-6, and CCL3.…”

Section: Discussionmentioning

confidence: 99%

Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies

et al. 2022

View full text Add to dashboard Cite

Respiratory tract infections (RTI) are mainly viral in origin and among the leading cause of childhood morbidity globally. Associated wheezing illness and asthma are still a clear unmet medical need. Despite the continuous progress in understanding the processes involved in their pathogenesis, preventive measures and treatments failed to demonstrate any significant disease-modifying effect. However, in the last decades it was understood that early-life exposure to microbes, may reduce the risk of infectious and allergic disorders, increasing the immune response efficacy. These results suggested that treatment with bacterial lysates (BLs) acting on gut microbiota, could promote a heterologous immunomodulation useful in the prevention of recurrent RTIs and of wheezing inception and persistence. This hypothesis has been supported by clinical and experimental studies showing the reduction of RTI frequency and severity in childhood after oral BL prophylaxis and elucidating the involved mechanisms. OM-85 is the product whose anti-viral effects have been most extensively studied in vitro, animal, and human cell studies and in translational animal infection/disease models. The results of the latter studies, describing the potential immune training-based activities of such BL, leading to the protection against respiratory viruses, will be reported. In response to human rhinovirus, influenza virus, respiratory syncytial virus and severe acute respiratory coronavirus-2, OM-85 was effective in modulating the structure and the functions of a large numbers of airways epithelial and immune cells, when administered both orally and intranasally.

show abstract

“…Recently, several studies have demonstrated the efficacy of bacterial immunotherapy using oral or mucosal formulations of polybacterial lysates (i.e., MV130 and OM85) for the prevention of viral wheezing illnesses or SARS-CoV2 infection [ 170 , 171 , 172 , 173 ]. Interestingly, in a clinical trial in children with wheezing attacks, sublingual treatment with MV130 showed safety and clinical efficacy against recurrent wheezing attacks [ 170 ].…”

Section: Current and Potential Therapeutics For Viral Infection In As...mentioning

confidence: 99%

“…Interestingly, in a clinical trial in children with wheezing attacks, sublingual treatment with MV130 showed safety and clinical efficacy against recurrent wheezing attacks [ 170 ]. In addition, using PMBCs from infants at high risk for asthma development, OM85 treatment primarily modulated gene networks triggered during innate immune responses to bacterial pathogens that typically accompany viral pathogens during severe lower respiratory infection [ 171 ]. As for SARS-CoV2 infection, OM-85 inhibited SARS-CoV-2 epithelial cell infection in vitro by downregulating the SARS-CoV-2 receptor, ACE2 expression, and TMPRSS2 transcription [ 172 ].…”

Section: Current and Potential Therapeutics For Viral Infection In As...mentioning

confidence: 99%

Viral Infection and Airway Epithelial Immunity in Asthma

Kim

2022

IJMS

View full text Add to dashboard Cite

Viral respiratory tract infections are associated with asthma development and exacerbation in children and adults. In the course of immune responses to viruses, airway epithelial cells are the initial platform of innate immunity against viral invasion. Patients with severe asthma are more vulnerable than those with mild to moderate asthma to viral infections. Furthermore, in most cases, asthmatic patients tend to produce lower levels of antiviral cytokines than healthy subjects, such as interferons produced from immune effector cells and airway epithelial cells. The epithelial inflammasome appears to contribute to asthma exacerbation through overactivation, leading to self-damage, despite its naturally protective role against infectious pathogens. Given the mixed and complex immune responses in viral-infection-induced asthma exacerbation, this review examines the diverse roles of airway epithelial immunity and related potential therapeutic targets and discusses the mechanisms underlying the heterogeneous manifestations of asthma exacerbations.

show abstract

Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studies

Cited by 15 publications

References 51 publications

Lycopene-Loaded Bilosomes Ameliorate High-Fat Diet-Induced Chronic Nephritis in Mice through the TLR4/MyD88 Inflammatory Pathway

Lycopene-Loaded Bilosomes Ameliorate High-Fat Diet-Induced Chronic Nephritis in Mice through the TLR4/MyD88 Inflammatory Pathway

Can bacterial lysates be useful in prevention of viral respiratory infections in childhood? The results of experimental OM-85 studies

Viral Infection and Airway Epithelial Immunity in Asthma

Contact Info

Product

Resources

About