Immune training enhances anti-viral responses and improves outcomes in Pax5−/+ mice susceptible to chronic infection

EMBO Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Abstract Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity ( −/+ ), resulting in reduced PAX5 levels mice, mimics germline somatic dysregulation contributing diseases such as childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). In contrast the well-characterized roles of during early development, little known about how impacts We infected mice with noncytopathic Lymphocytic Choriomeningitis Virus (LCMV) and found infection chronic Docile strain resulted decreased survival mice. While adaptive CD8 + T-cell (CTL) immunity was robust LCMV-specific neutralizing antibody production compromised leading impaired long-term viral clearance pro-inflammatory milieu bone marrow (BM). Here we show outcomes were improved upon prophylactic treatment β-glucan trainer through induction heterologous protection against infection. β-Glucan enhanced clearance, CTL immunity, monocyte immunosuppression multiple LCMV-resident host organs. New insight from this study will help design effective strategies infections, particularly genetically predisposed susceptible hosts.

Язык: Английский

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Deconvoluting the interplay of innate and adaptive immunity in BCG-induced nonspecific and TB-specific host resistance

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)

Опубликована: Фев. 28, 2025

BCG is the oldest vaccine in continuous use. While current intradermal vaccination regimens confer limited protection outside context of pediatric extrapulmonary tuberculosis (TB), promising new data indicate that when administered mucosally or intravenously at a higher dose, can induce sterilizing immunity against pulmonary TB nonhuman primates. also known to promote nonspecific host resistance variety unrelated infections and standard immunotherapy for bladder cancer, suggesting this innate immune function may contribute its protective role TB. Here, we propose both mycobacterial-specific off-target effects depend on interplay adaptive cells cytokines they produce, elucidation interaction should be major strategy development more effective BCG-based vaccines immunotherapies.

Язык: Английский

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Bacillus Calmette-Guérin immunotherapy induces an efficient antitumor response to control murine melanoma depending on MyD88 signaling

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 21, 2024

Bacillus Calmette-Guérin (BCG) is the first line treatment for bladder cancer and it also proposed melanoma immunotherapy. BCG modulates tumor microenvironment (TME) inducing an antitumor effective response, but immune mechanisms involved still poorly understood. The profile of B16-F10 murine cells was assessed by infecting these with or stimulating them agonists different innate pathways such as TLRs, inflammasome, cGAS-STING type I IFN. did not respond to any those stimuli, except IFN agonists, contrasting bone marrow-derived macrophages (BMDMs) that showed high production proinflammatory cytokines. Additionally, we confirmed able infect B16-F10, which in turn can activate spleen from mice co-culture experiments. Furthermore, established a subcutaneous model intratumoral compared wild TLR2 -/- , TLR3 TLR4 TLR7 TLR3/7/9 caspase 1 11 IL-1R cGAS STING IFNAR MyD88 deficient animals. These results vivo demonstrate signaling important immunotherapy control mice. Also, fails induce cytokine experiments using BMDMs derived wild-type (WT) Immunotherapy recruitment inflammatory TME mice, impairing IFN-γ T cells. In conclusion, impacts on both adaptive responses leading efficient response against melanoma.

Язык: Английский

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Role of trained innate immunity against mucosal cancer

Current Opinion in Virology, Год журнала: 2024, Номер 64, С. 101387 - 101387

Опубликована: Фев. 1, 2024

Язык: Английский

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The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 27, 2024

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known affect disease severity. Yet, how the inflammatory milieu of lung at time exposure impacts control viral replication remains poorly understood. We demonstrate here that immune events in mouse closely preceding significantly impact we identify key innate pathways required limit replication. A diverse set pulmonary stimuli, including resolved antecedent respiratory infections with

Язык: Английский

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