The role of eosinophil and migratory dendritic cell (migDC) subsets during tropical pulmonary eosinophilia (TPE), a potentially fatal complication of lymphatic filariasis, has not been explored. We show that the onset of TPE is characterized by the accumulation of ROS and anaphylatoxins and a rapid influx of morphologically distinct Siglec-Fint resident eosinophils (rEos) and Siglec-Fhi inflammatory eosinophils (iEos) in the lungs, BAL fluid, and blood of TPE mice. While rEos display regulatory behavior, iEos are highly inflammatory cells, as evident in upregulated expression of activation markers CD69 and CD101, anaphylatoxin receptor C5AR1, alarmins s100a8 and s100a9, components of NADPH oxidase, and copious secretion of TNF-α, IFN-γ, IL-6, IL-1β, IL-4, IL-10, IL-12, and TGF-β. Importantly, iEos exhibited heightened ROS generation, higher phagocytic and increased antigen presentation capacity, elevated Ca2+ influx, and increased F-actin polymerization but downregulated negative regulators of the immune response, i.e., Cd300a, Anaxa1, Runx3, Lilrb3, and Serpinb1a, underlining their essential role in promoting lung damage during TPE. Interestingly, TPE mice also showed significant expansion of CD24+CD11b+ migDCs, which showed upregulated expression of maturation and costimulatory markers CD40, CD80, CD83, CD86, and MHCII, increased antigen presentation capacity, and higher migratory potential as evidenced by increased expression of cytokine receptors CCR4, CCR5, CXCR4, and CXCR5. CD24+CD11b+ migDCs also upregulated the expression of immunoregulators PD-L1 and PD-L2 and secreted proinflammatory cytokines, suggesting their significant involvement during TPE. Taken together, we document important morphological, immunophenotypic, and functional characteristics of eosinophil and migDC subsets in the lungs of TPE mice and suggest that they contribute to worsening lung histopathological conditions during TPE.
Keywords: anaphylatoxins; filariasis; inflammatory eosinophils (iEos); migratory dendritic cells (migDCs); resident eosinophils (rEos); tropical pulmonary eosinophilia (TPE).