Impact of human filarial infections on the metabolic and immunological profile and characterization of filariae-induced tropical pulmonary eosinophilia using a newly established mouse model

Abstract

Parasitic filarial infections occur in tropical areas and cause debilitating diseases. In this thesis, two aspects were investigated: I) The development of tropical pulmonary eosinophilia in a novel mouse model and II) beneficial effects of filarial infections on the metabolic and immunological profile in an open-label pilot trial that was conducted in the rural Northwest of Cameroon. A mouse model for tropical pulmonary eosinophilia (TPE) was established using the rodent filarial nematode Litomosoides sigmodontis. The model demonstrated immunological and histopathological features that are closely associated with human TPE, i.e., eosinophilia, microfilariae clearance from the blood and increased retention in the lung tissue. TPE mice had increased IgE as well as serum IL-5. These effects where partly dependent on eosinophils. Blocking IL-33 signaling during TPE, decreased the type 2 shift, eosinophilia, eosinophil activation and alleviated lung lacunarity. In conclusion, this demonstrates that eosinophils and IL-33 signaling are essentially involved in the development of TPE and inhibiting IL-33 signaling might be a potent target to intervene in microfilariae- and potentially eosinophil-derived lung pathology. <br /> In the second part of this thesis, a trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. Lean (BMI<25), overweight (BMI >25 and <30) and clinically obese (BMI =30) participants infected with Mansonella perstans, Onchocerca volvulus or Loa loa from Littoral regions of Cameroon were evaluated for their parasitological, immunological, metabolic, anthropomorphic measurements and biochemical profile before and after treatment of their parasitic infections. <br /> The results suggest that some filarial infections improve clinical parameters compared to uninfected endemic individuals, e.g., circulating enzymes that predict liver function and markers for kidney associated diseases were partly decreased. Participants with filarial infections showed significantly decreased serum levels of C-reactive protein and glycated hemoglobin, indicating a decrease of systemic inflammation, metabolic inflammation and improved lipid hemostasis. <br /> Moreover, prevalence of type 2 diabetes was 2.3 times higher amongst the endemic normal population compared to the filarial infected participants. Taken together, the data presented here suggests that filarial infections may positively impact low-grade inflammation and metabolic parameters and therefore protect against the development of type 2 diabetes.