Pulmonary granuloma formation during latentCryptococcus neoformansinfection in C3HeB/FeJ mice involves progression through three immunological phases DOI Open Access
Jovany J. Betancourt, Minna Ding, J. Marina Yoder

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little known about immunological conditions establishing latent granuloma lungs. To investigate this, we performed an analysis cell populations, cytokine changes, during with disease-causing clinical isolate C3HeB/FeJ mice over 360 days. We found latently infected progress through three phases where different profiles dominate: early phase characterized by eosinophilia, high IL-4/IL-13,

Language: Английский

Pulmonary granuloma formation during latent Cryptococcus neoformans infection in C3HeB/FeJ mice involves progression through three immunological phases DOI Creative Commons
Jovany J. Betancourt, Minna Ding, J. Marina Yoder

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Cryptococcus neoformans is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little known about immunological conditions establishing latent granuloma lungs. To investigate this, we performed an analysis cell populations, cytokine changes, during with disease-causing clinical isolate C3HeB/FeJ mice over 360 days. We found latently infected progress through three phases where different profiles dominate: early phase characterized by eosinophilia, high IL-4/IL-13, C. proliferation lungs; intermediate multinucleated giant formation, IL-1α/IFNγ, expansion, increased blood antigen levels; late significant expansion T cells, condensation, decreases lung burden levels. These findings highlight complex series changes occur establishment granulomas lungs lay foundation for studies to identify critical beneficial responses infections.IMPORTANCECryptococcus disseminates from brain fatal Latent controlled organized collections cells called granulomas. The structure are poorly understood due inconsistent human pathology results disagreement between necrotic granuloma-forming rat models non-necrotic mouse models. overcome investigated strain which forms response other pathogens. progresses described early, intermediate, granulomatous characteristics. Ultimately, show form could provide novel model profiles.

Language: Английский

Citations

0
Microenvironments of tuberculous granuloma: advances and opportunities for therapy DOI Creative Commons

G. R. F. Krueger,

Shah Faisal,

Anca Dorhoi

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 24, 2025

The hallmark tissue lesions of tuberculosis (TB) are granulomas. These multicellular structures exhibit varying degrees cellular complexity, dynamic, and show considerable diversity within between hosts. Categorization based on gross pathologic features, particularly caseation necrosis, was historically coined prior to the identification mycobacteria as causative agent TB. More recently, granuloma zonation immune cell composition, metabolite abundance, physical characteristics has gained attention. With advent single-cell analyses, distinct microenvironments ecosystems TB granulomas have been identified. We summarize architecture highlight their heterogeneity, including niches well factors such oxygen gradients that modulate lesion fate. discuss opportunities for therapy, highlighting new models power in silico modeling unravel features trajectories. Understanding relevance microenvironment disease pathophysiology will facilitate development more effective interventions, host-directed therapies

Language: Английский

Citations

0
Host and pathogen genetic diversity shape vaccine-mediated protection to Mycobacterium tuberculosis DOI Creative Commons
Sara Cohen, Courtney R. Plumlee,

Lindsay Engels

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 28, 2024

To investigate how host and pathogen diversity govern immunity against Mycobacterium tuberculosis (Mtb), we performed a large-scale screen of vaccine-mediated protection aerosol Mtb infection using three inbred mouse strains [C57BL/6 (B6), C3HeB/FeJ (C3H), Balb/c x 129/SvJ (C129F1)] (H37Rv, CDC1551, SA161) representing two lineages distinct virulence properties. We compared protective modalities, all which involve inoculation with live mycobacteria: Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, delivered either subcutaneously or intravenously, concomitant (CoMtb), model pre-existing in low-level is established cervical lymph node following intradermal inoculation. examined lung bacterial burdens at early (Day 28) late 98) time points after challenge histopathology Day 98. observed substantial heterogeneity reduction load afforded by these modalities 28 across combinations noted strong positive correlation between burden unvaccinated mice degree vaccination. Although variation nine mouse/bacterium strain combinations, virtually similarly for given strain-strain combination. also dramatic changes driven both genetic backgrounds. Vaccination improved pathology scores infections except CDC1551. However, most impact vaccination on lesion development occurred C3H-SA161 combination, where entirely abrogated large necrotic lesions that arise mice. In conclusion, find can be recapitulated introducing variability genetics, resulting as measured well histopathology. These differences harnessed future studies to identify immune correlates vaccine efficacy.

Language: Английский

Citations

2
APOE Protects Against Severe Infection with Mycobacterium tuberculosis by Restraining Production of Neutrophil Extracellular Traps DOI Creative Commons
Dong Liu, Dat Mai, Ana N. Jahn

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

While neutrophils are the predominant cell type in lungs of humans with active tuberculosis (TB), they relatively scarce most strains mice that used to study disease. However, similar humans, account for approximately 45% CD45+ cells

Language: Английский

Citations

0
Pulmonary granuloma formation during latentCryptococcus neoformansinfection in C3HeB/FeJ mice involves progression through three immunological phases DOI Open Access
Jovany J. Betancourt, Minna Ding, J. Marina Yoder

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little known about immunological conditions establishing latent granuloma lungs. To investigate this, we performed an analysis cell populations, cytokine changes, during with disease-causing clinical isolate C3HeB/FeJ mice over 360 days. We found latently infected progress through three phases where different profiles dominate: early phase characterized by eosinophilia, high IL-4/IL-13,

Language: Английский

Citations

0