Host genetic background is a barrier to broadly effective vaccine protection: Relevance to BCG and<i>Mycobacterium tuberculosis</i>Infection

Lai, Rocky; Gong, Diana; Williams, Travis; Ogunsola, Abiola F; Cavallo, Kelly; Arlehamn, Cecilia S. Lindestam; Beamer, Gillian; Ferris, Martin T.; Sassetti, Christopher M.; Lauffenburger, Douglas A.; Behar, Samuel M.

doi:10.1101/2022.09.19.508548

Cited by 2 publications

(2 citation statements)

References 40 publications

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“…H37Rv expressing yellow fluorescent protein (YFP) has been previously described 9, 42 . The mice were exposed to an aerosolized inoculum of Rv.YFP using a Glas-Col Inhalation Exposure System (Glas-Col LLC, Terre Haute, IN) as described 34, 43 . The number of M. tuberculosis deposited in the lungs was determined for each experiment and varied ranging between 37–90 CFU.…”

Section: Methodsmentioning

confidence: 99%

Heterogeneity in lung macrophage control ofMycobacterium tuberculosisis determined by T cells

Lai,

Williams,

Rakib

et al. 2023

Preprint

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FollowingMycobacterium tuberculosisinfection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution ofM. tuberculosisamong different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminateM. tuberculosisinfection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.

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Section: Methodsmentioning

confidence: 99%

Heterogeneity in lung macrophage control ofMycobacterium tuberculosisis determined by T cells

Lai,

Williams,

Rakib

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Without doubt, KO models have substantially enriched the knowledge about immune cells and immune pathways in TB and provided causality proofs for disease pathogenesis. Embracing genetic diversity by usage of CC line and DO mice offers unique opportunities for mechanistic studies and may provide new ways to guide TB prophylaxis ( 92 ).…”

Section: Small Animal Modelsmentioning

confidence: 99%

Animal models for COVID-19 and tuberculosis

et al. 2023

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Respiratory infections cause tremendous morbidity and mortality worldwide. Amongst these diseases, tuberculosis (TB), a bacterial illness caused by Mycobacterium tuberculosis which often affects the lung, and coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), stand out as major drivers of epidemics of global concern. Despite their unrelated etiology and distinct pathology, these infections affect the same vital organ and share immunopathogenesis traits and an imperative demand to model the diseases at their various progression stages and localizations. Due to the clinical spectrum and heterogeneity of both diseases experimental infections were pursued in a variety of animal models. We summarize mammalian models employed in TB and COVID-19 experimental investigations, highlighting the diversity of rodent models and species peculiarities for each infection. We discuss the utility of non-human primates for translational research and emphasize on the benefits of non-conventional experimental models such as livestock. We epitomize advances facilitated by animal models with regard to understanding disease pathophysiology and immune responses. Finally, we highlight research areas necessitating optimized models and advocate that research of pulmonary infectious diseases could benefit from cross-fertilization between studies of apparently unrelated diseases, such as TB and COVID-19.

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Host genetic background is a barrier to broadly effective vaccine protection: Relevance to BCG andMycobacterium tuberculosisInfection

Cited by 2 publications

References 40 publications

Heterogeneity in lung macrophage control ofMycobacterium tuberculosisis determined by T cells

Heterogeneity in lung macrophage control ofMycobacterium tuberculosisis determined by T cells

Animal models for COVID-19 and tuberculosis

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