Marmoset monkeys (Callithrix jacchus) develop eosinophilic airway inflammation after house dust mite exposure

Dahlmann, F.; Curths, C.; Wichmann, J.; Jimenez Delgado, S.; Twisterling, E.; Kap, Y. S.; van Driel, N.; t Hart, B. A.; Knauf, Y.; Becker, T.; Dunker, S.; Windt, H.; Bleyer, M.; Kaup, F.-J.; Sewald, K.; Braun, A.; Knauf, S.

doi:10.1101/2020.02.24.962498

bioRxiv · 10.1101/2020.02.24.962498

Marmoset monkeys (Callithrix jacchus) develop eosinophilic airway inflammation after house dust mite exposure

Dahlmann, F.·Curths, C.·Wichmann, J.·Jimenez Delgado, S.·Twisterling, E.·Kap, Y. S.·van Driel, N.·t Hart, B. A.·Knauf, Y.·Becker, T.·Dunker, S.·Windt, H.·Bleyer, M.·Kaup, F.-J.·Sewald, K.·Braun, A.·Knauf, S.

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Abstract

BackgroundExtensive analysis of eosinophilic airway inflammation in human-relevant animal models is required to test novel, human-specific pharmaceuticals. This requires species, which show high genetic homology to humans such as non-human primates. Efficacy assessment of novel human-specific biologicals in eosinophilic airway inflammation is currently performed in the cost-intensive macaque asthma model. ObjectiveThe present study investigated whether marmoset monkeys (Callithrix jacchus), a small-bodied non-human primate species from the New World, develop eosinophilic airway inflammation in response to house dust mite allergen exposure (HDM, Dermatophagoides pteronyssinus). MethodsMarmoset monkeys were sensitized against HDM by subcutaneous (s.c.) injection and subsequent intratracheal (i.t.) HDM aerosol challenges. Airway and systemic immunologic reactions were monitored and sensitivity towards glucocorticoid therapy was assessed. The pulmonary immunologic response was analyzed by repetitive bronchoalveolar lavage (BAL). ResultsBronchoalveolar lavage fluid (BALF) exhibited increased levels of eosinophils, mast cells, and lymphocytes, as well as interleukin (IL)-13 after HDM challenges, compared to negative controls. The systemic immunologic response was assessed in peripheral blood mononuclear cells derived from sensitized animals, which secreted increased IL-13 and IFN-{gamma} upon allergen stimulation in contrast to non-sensitized negative control animals. Although IgE was not detectable, HDM-specific serum IgG was elevated in sensitized animals. Both airway and systemic responses were reduced by treatment with glucocorticoids. However, lung function and pathological analyses did not reveal significant differences between groups. ConclusionIn conclusion, marmoset monkeys developed a mild HDM-induced eosinophilic airway inflammation useful for efficacy testing of novel human-specific biologicals.

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Dahlmann, F., Curths, C., Wichmann, J., Jimenez Delgado, S., Twisterling, E., Kap, Y. S., van Driel, N., t Hart, B. A., Knauf, Y., Becker, T., Dunker, S., Windt, H., Bleyer, M., Kaup, F.-J., Sewald, K., Braun, A., Knauf, S.. 2020-02-24. Marmoset monkeys (Callithrix jacchus) develop eosinophilic airway inflammation after house dust mite exposure. https://doi.org/10.1101/2020.02.24.962498

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