Cobalt exposure via skin alters immune cells in lung and enhances
pulmonary responses to cobalt in a mouse model
Abstract
Background: Cobalt has been associated with allergic contact dermatitis
and occupational asthma. However, the link between skin exposure and
lung responses to cobalt is currently unknown. We investigated the
effect of prior dermal sensitization to cobalt on pulmonary
physiological and immunological responses after subsequent challenge
with cobalt via the airways. Methods: BALB/c mice received epicutaneous
applications (25 μl/ear) with 5%
CoCl2*6H2O (Co) or the vehicle (Veh)
dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal
challenges with 0.05% CoCl2*6H2O or
saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh,
Veh/Co and Co/Co. To detect early respiratory responses non-invasively,
we performed sequential in vivo micro-computed tomography (µCT). One day
after the last challenge, we assessed airway hyper-reactivity (AHR) to
methacholine, inflammation in bronchoalveolar lavage (BAL), innate
lymphoid cells (ILCs) and dendritic cells (DCs) in lung, and serum IgE.
Result: Compared with the Veh/Veh-group, the Co/Co-group showed
increased µCT-derived lung response, increased AHR to methacholine,
mixed neutrophilic and eosinophilic inflammation, elevated monocyte
chemoattractant protein-1 (MCP-1) and elevated keratinocyte
chemoattractant (KC) in BAL. Flow cytometry in the Co/Co-group
demonstrated increased DC, type 1 and type 2 conventional DC
(cDC1/cDC2), monocyte-derived DC, increased ILC group 2 and NCR-ILC
group 3. The Veh/Co-group showed only increased AHR to methacholine and
elevated MCP-1 in BAL, whereas the Co/Veh-group showed increased cDC1
and ILC2 in lung. Conclusion: We conclude that dermal sensitization to
cobalt may increase the susceptibility of the lungs to inhaling cobalt.
Mechanistically, this enhanced susceptibility involves changes in
pulmonary DCs and ILCs.