Comparison of immune responses to Loa loa stage-specific antigen extracts in Loa loa -exposed BALB/c mice upon clearance

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Parasites & Vectors Open Access

RESEARCH

Comparison of immune responses to Loa loa stage‑specific antigen extracts in Loa loa‑exposed BALB/c mice upon clearance of infection Valerine C. Chunda1,2†, Manuel Ritter3*†  , Ayukenchengamba Bate1,2, Narcisse V. T. Gandjui1,2, Mathias E. Esum1,2, Fanny F. Fombad1,2, Abdel J. Njouendou1,2, Patrick W. C. Ndongmo1,2, Mark J. Taylor4, Achim Hoerauf3,5, Laura E. Layland3,5, Joseph D. Turner4 and Samuel Wanji1,2

Abstract  Background:  Different immune mechanisms are capable of killing developmental stages of filarial nematodes and these mechanisms are also likely to vary between the primary and a challenge infection. However, the lack of a detailed analysis of cytokine, chemokine and immunoglobulin levels in human loiasis is still evident. Therefore, detailed analysis of immune responses induced by the different developmental stages of Loa loa in immune-competent BALB/c mice will aid in the characterization of distinct immune responses that are important for the immunity against loiasis. Methods:  Different developmental stages of L. loa were obtained from human peripheral blood (microfilariae, MF), the transmitting vector, Chrysops (larval stage 3, L3) and infected immune-deficient BALB/cRAG2γc−/− mice (L4, L5, adult worms). Groups of wildtype BALB/c mice were then injected with the isolated stages and after 42 days postinfection (pi), systemic cytokine, chemokine and immunoglobulin levels were determined. These were then compared to L. loa-specific responses from in vitro re-stimulated splenocytes from individual mice. All parameters were determined using Luminex technology. Results:  In a pilot study, BALB/c mice cleared the different life stages of L. loa within 42 days pi and systemic cytokine, chemokine and immunoglobulin levels were equal between infected and naive mice. Nevertheless, L. loa-specific re-stimulation of splenocytes from mice infected with L5, MF or adult worms led to induction of Th2, Th17 and chemokine secretion patterns. Conclusions:  This study shows that although host immunity remains comparable to naive mice, clearance of L. loa life-cycle development stages can induce immune cell memory leading to cytokine, chemokine and immunoglobulins secretion patterns which might contribute to immunity and protection against reinfection. Keywords:  Recall immune responses, Re-stimulation, Immunoglobulins, Chemokines, Cytokines, Microfilariae, Adult worms, Larvae, Loa loa antigen extract

*Correspondence: [email protected]‑bonn.de; [email protected] † Valerine C. Chunda and Manuel Ritter contributed equally to this work 3 Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), Medical Faculty, University of Bonn, Bonn, Germany Full list of author information is available at the end of the article

Background Loiasis is caused by the filarial nematode Loa loa that is endemic in equatorial rainforest regions of Central and West Africa. As with other filariae, humans are infected

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