Publikationsdatenbank

Low-intensity ascaris infections impact growth, immune responses, ferritin levels, and microbial homeostasis in schoolchildren and suppress NK cell functionality in domestic pig as a human-relevant animal model (2025)

Art

Hochschulschrift

Autor

Mugo, Robert Mugendi (WE 6)

Quelle

Berlin, 2025 — 122 Seiten

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/47933

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Background: Despite the control efforts, ascariasis remains a major public health concern. The introduction of regular preventive chemotherapy (PC) in endemic regions has led to a shift from high- to low-intensity Ascaris infections. These infections cannot be reliably detected by the standard diagnostic methods and thus act as reservoirs for sustained transmission. Furthermore, although the detrimental impacts of high-intensity Ascaris infections on nutrition, immunity, growth, and intellectual capacity are well established, both the short- and long-term impacts of low-intensity infections remain unknown. Additionally, Ascaris coexist in a dynamic interplay with the gut bacteria which are also linked to immune function and host metabolism. These interactions highlight the need to comprehensively examine Ascaris infections beyond their direct pathological effects, considering their broader impact on nutrition, microbiome and immune homeostasis. To address these gaps, we aimed to investigate the integrated effects of low-intensity Ascaris infections on nutrition, immunity and microbiome in schoolchildren living in an endemic setting. Additionally, by using the domestic pig as a human-relevant animal model, we aimed to gain preliminary insights into the natural killer (NK) cells functional disruptions triggered by a low-dose Ascaris infection and its potential to alter host susceptibility to Salmonella. Specifically, we aimed to: 1. Assess the diagnostic performance of copromicroscopy, multiplex-qPCR, and serology in the detection of low-intensity Ascaris infections. 2. Investigate the immune alterations associated with low-intensity Ascaris infections. 3. Determine the nutritional consequences of low-intensity Ascaris infections. 4. Analyze the gut microbiota composition and its associations with low-intensity Ascaris infection, immune responses, and nutritional status. 5. Evaluate how low-dose Ascaris infection modulates NK cell function in domestic pigs as a human-relevant model, to inform mechanisms relevant to human health outcomes during common coinfections in Ascaris-endemic human populations. Results: To precisely detect low-intensity Ascaris infections, we developed and optimized a multiplex-qPCR assay, which exhibited superior sensitivity compared to conventional microscopic techniques. Additionally, we identified IgG1 and IgG4 antibodies against adult Ascaris excretory-secretory products as potential accurate serological markers for current Ascaris infections and exposure, owing to their high accuracy and sensitivity, respectively. We observed a high prevalence of low-intensity Ascaris infections among schoolchildren four months following the administration of STH PC. The children's diet was predominantly carbohydrate-based with a low intake of protein-rich foods. Notably, we identified a relatively high prevalence of protein-energy malnutrition, reflected in low albumin levels, stunting and thinness, particularly among boys. Low-intensity Ascaris infections were negatively associated with zbfa (thinness) and zhfa (stunting) as well as ferritin levels. We show that Ascaris infection is associated with systemic memory CD4 responses, characterised by enhanced gut-homing capacity and a mixed Th1/Th2/Th17 cytokine profile and a mixed IgM/IgG/IgA/IgE antibody response. Notably, Ascaris-specific mucosal IgA1 responses correlated with Oscillospiraceae, Dorea formicigenerans, and Prevotella species which are all short-chain fatty acid-producing gut bacteria taxa known for their immunomodulatory properties. These microbial taxa were also linked to ferritin levels. Furthermore, we demonstrate that a low-dose Ascaris infection significantly impairs NK cells cytokine production and cytotoxicity both in the lungs and in the systemic circulation by altering transcription factors balance and upregulating inhibitory receptors. Conclusion: This study highlights the adverse effects of low-intensity Ascaris infections on nutrition, growth, and immunity. Low-intensity Ascaris infections may also modulate the gut microbiome indirectly by altering ferritin levels and mucosal immunity to foster specific microbial shifts. The profound suppression of NK cell functions by a low-dose Ascaris infection and during Ascaris-Salmonella coinfection indicate that Ascaris infection increases host susceptibility to coinfections and potentially influences disease outcomes. Our findings underscore the urgent need for highly sensitive diagnostic tools such as qPCR and serological markers to accurately ascertain the true burden of Ascaris infections. Future research should prioritize longitudinal human and parallel pig studies to understand the long-term impacts of low-intensity Ascaris infections and their broader implications for coinfections and disease outcomes in children to inform evidence-based interventions.