Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice

Abstract

Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose-and timedependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro-(TNFa, IL-6, IL-1b) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes <5% at all timepoints or concentrations. Granulomatous inflammation peaked between 8 and 24 h post-exposure, and resolved by 96 h. Live bacterial challenge, typically encountered in real-world exposures, showed no significant differences from bacterial lysate except for induction of appreciable levels of interferon (IFN)-c, implying additional immunogenic potential. Collectively, the short-term mycobacterial challenge in mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter-and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease. ARTICLE HISTORY

Clinical Features of Hypersensitivity Pneumonitis in Children: A Single Center Study

“…HP is an immune-mediated ILD that occurs in genetically susceptible individuals after repeated inhalation of organic antigens (such as fungi, bacteria, and animal and insect proteins), which may lead to an immune response to acute lung inflammation ( 16 ). It is characterized by recruitment of granulocytes as well as T cells and B cells ( 17 ).…”

Release of Interleukin-1β evaluation among mineral oil mist‐exposed workers

“…M-Oil is not only made of a variety of organic and inorganic chemicals, lubricant, biocides and biocide residues, metal insoluble, and fine particulate, but also made of bio-aerosol, which are the stimuli of the immune reaction (Gilbert et al, 2010; Barber et al, 2011). There are several reports on studying immunological responses caused by M-Oil exposure (Johansson et al, 2017; Gordon et al, 2006; Roussel et al, 2011; Thorne et al, 2006). Although clinical inflammation symptoms were reported repeatedly (Fishwick et al, 2005; Rosenman, 2009), a limited number of publications studied the release of cytokine parameters in the occupational exposure.…”

Clinical and morphological characteristics of hypersensitivity pneumonitis

“…Для того чтобы произошла депозиция антигена в мелких дыхательных путях и альвеолах, антиген должен иметь размеры менее 5 мкм, хотя возможно развитие заболевания и при абсорбции растворимых антигенов из частиц больших размеров, осевших в проксимальных отделах бронхиального дерева. Ключевую роль в патогенезе заболевания играют процесс сенсибилизации к антигену и появление клинических симптомов после повторного воздействия антигена [18]. ГП справедливо считается иммунопатологическим заболеванием, в развитии которого ведущая роль принадлежит аллергическим реакциям 3-го и 4-го типа (по классификации Gell, Coombs, 1969).…”