Immunophenotypic and Functional Characterization of Eosinophil and Migratory Dendritic Cell Subsets during Filarial Manifestation of Tropical Pulmonary Eosinophilia

Abstract

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.

Identification and Characterization of a Novel Nematode Pan Allergen (NPA) fromWuchereria bancroftiand their Potential Role in Human Filarial Tropical Pulmonary Eosinophilia (TPE)

“…The NPA gene have not been annotated previously from any nematode parasites, and this this is the first report on a pan allergen. IgE, eosinophils and allergy are hallmarks of nematode parasitic infections and TPE [31]. We believe that the NPA could play a major role in triggering the allergic responses in the host during parasitic larval invasion.…”

Repeated sensitization of mice with microfilariae of Litomosoides sigmodontis induces pulmonary eosinophilia in an IL-33-dependent manner

“…Similarly, Gang et al recently demonstrated that a similar increase in inflammatory eosinophils occurs in the TPE Brugia spp . model [ 55 ], which could indicate that these eosinophils might be associated with lung hyper-responsiveness, MF clearance and potentially lung pathology. Accordingly, tissue repair mechanisms, i.e., release of AREG and enhanced matrix metalloprotease activity in ELD mice of our study suggest that the loss of lung tissue integrity could be caused by a prolonged repair mechanism and fibrosis which was dependent on eosinophils and IL-33 signaling.…”

Identification and characterization of a novel nematode pan allergen (NPA) from Wuchereria bancrofti and their potential role in human filarial tropical pulmonary eosinophilia (TPE)

“…The NPA gene have not been annotated previously from any nematode parasites, and this this is the first report on a pan allergen. IgE, eosinophils and allergy are hallmarks of nematode parasitic infections and TPE [ 32 ]. We believe that the NPA could play a major role in triggering the allergic responses in the host during parasitic larval invasion.…”