Human Neuroimmune Response Against Angiostrongylus Cantonensis

David Gómez-Pérez; Christian Meijides-Mejías Meijides-Mejías; Alberto Juan Dorta-Contreras

Human neuroimmune response against angiostrongylus cantonensis

Short Comunications

Human neuroimmune response against angiostrongylus cantonensis

David Gómez-Pérez¹*
Christian Meijides-Mejías¹
Alberto Juan Dorta-Contreras¹

¹Laboratorio Central de Líquido Cefalorraquídeo (LABCEL) Facultad de Ciencias Médicas Miguel Enríquez, Universidad de Ciencias Médicas de la Habana, Cuba.

*Author for correspondence. E-mail:agongora@infomed.sld.cu

ABSTRACT

Introduction: Angiostrongylus cantonensis is a zoonotic pathogen that causes human angiostrongyliasis; its main clinical manifestation is eosinophilic meningitis. It was reported in Cuba for the first time in America.
Objetive: To review the main immunological findings about the human neuroimmune response against this parasite.
Methods: This paper is based on a review of the papers mainly from Cuban authors published in the last 10 years about the human neuroimmune response against this helmint. This information becomes more relevant after the introduction of the African giant snail Lissachatina fulica in Cuba in 2014.
Results:The humoral immune response is based on the immunoglobulin intrathecal synthesis. When the third-stage larvae goes to the central nervous system at the first lumbar puncture there are no major immunoglobulin synthesis. One week later an immune intrathecal response is done by a two class major immunoglobulin class mainly IgG+ IgA. Intrathecal activation of complement is evident of intrathecal synthesis of major immunoglobulins during this disease. The activation of complement system components in cerebrospinal fluid is relevant to the understanding of this tropical disease, which is emerging in the Western hemisphere. Intrathecal synthesis of at least one of the major immunoglobulins and a wide spectrum of patterns may be observed. Although intrathecal synthesis of C3c and IgE is always present, C4 intrathecal synthesis does not occur in every patient. The diversity of intrathecal synthesis and activation of the different complement pathways enables their division into three variant groups. In each one could be find the activation of one or several complement pathways including the participation of MBL, MASP-2 and ficolins as part of the lectin pathway complement activation.
Conclusions: The neuroimmune response against Angiostrongylus cantonensis eosinophilic meningoencephalitis is an example of the host-parasite interaction.

INTRODUCTION

The helmint Angiostrongylus cantonensis was first reported in America in Cuba in 1981. Since these date up to now there are a group of Cubans researchers that are devoted to discover how the human as erratic host could develops its immune response in the central nervous system. This parasite produces an eosinophilic meningoencephalitis.(1)

METHODS

This paper is based on a review of the papers mainly from Cuban authors published in the last 10 years about the human neuroimmune response against this helmint. This information becomes more relevant after the introduction of the African giant snail Lissachatina fulica in Cuba in 2014.

RESULTS

The humoral immune response is based on the immunoglobulin intrathecal synthesis. When the third-stage larvae go to the central nervous system at the first lumbar puncture there are no major immunoglobulin syntheses.

One week later an immune intrathecal response is done by a two class major immunoglobulin class mainly IgG+ IgA. It can be observed in the corresponding reibergram. (Figure 1)(1)

In the first lumbar puncture it is possible to find IgE (2) and C3c (3) (Figure 2) intrathecal synthesis and with the major immunoglobulins reibergrams can be an auxiliary method of human angiostrongyloidosis diagnosis.

Intrathecal activation of complement is evident of intrathecal synthesis of major immunoglobulins during the acute phase of the disease.

The activation of complement system components in cerebrospinal fluid is relevant to the understanding of this tropical disease, which is emerging in the Western hemisphere.

Intrathecal synthesis of at least one of the major immunoglobulins and a wide spectrum of patterns may be observed. Although intrathecal synthesis of C3c and IgE is always present, C4 intrathecal synthesis does not occur in every patient. (Figure 2)(4)

The diversity of intrathecal synthesis and activation of the different complement pathways enables their division into three variant groups.(5) In each one could be find the activation of one or several complement pathways.

In the lectin pathway complement activation MBL constitutes one of the five initiators. It was possible to quantify the intrathecal synthesis of MBL by using the corresponding reibergram. (Figure 2). Also it was reported three pediatric patients suffering from Angiostrongylus cantonensis meningoencephalitis that has a MBL deficiency.(6)

In addition H-ficolin and M-ficolin intrathecal synthesis was observed in patients with this helminthiasis that affect the central nervous system.(7)

In Table 1 it is possible to found the list of the published papers from 2009 to 2018.

CONCLUSIONS

The neuroimmune response against Angiostrongylus cantonensis eosinophilic meningoencephalitis is an example of the host-parasite interaction.

Table 1. Last papers from LABCEL published from 2009-2018

Angiostrongyliasis in the Americas. Emerg Infect Dis 2009;15: 991.Alberto Juan Dorta-Contreras, María Esther Magraner-Tarrau, Eduardo Sánchez Zulueta	2009
Activación y biosíntesis intratecal de C3c en niños con meningoencefalitis eosinofílica por Angiostrongylus cantonensis.Rev Neurol. 2009; 48:632-5. Bárbara Padilla-Docal, Alberto Juan Dorta-Contreras, Raisa Bu Coifiu-Fanego.
Padilla-Docal B, Dorta-Contreras AJ, Bu-Coifiu-Fanego R, Rodríguez-Rey A, Gutiérrez-Hernández JC, de Paula-Almeida SO. Reibergram of intrathecal synthesis of C4 in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis. Am J Trop Med Hyg 2010; 82(6):1094-8.	2010
Neuroimmunological findings from the first report of Angiostrongylus cantonensis outbreak in Ecuador[abstract] Int J Infect Dis 2010;14S1: 76.023.A. J. Dorta-Contreras1, B. Padilla-Docal, J. M. Moreira, L. Martini Robles, J. Muzzio Aroca, F. Alarcon, R. Bu Coifiu Fanego.
Dos casos de meningitis crónica por Angiostrongylus cantonensis. Rev Neurol 2011; 52 (1): 60-1. Domingo Sabina-Molina, Alberto J. Dorta- Contreras, Bárbara Padilla-Docal, Raisa Bu-Coifiú Fanego.	2011
Padilla-Docal B, Dorta-Contreras AJ, Moreira JM, Martini-Robles L,Muzzio-Aroca J, Alarcón F, Magraner-Tarrau ME, Bu-Coifiu-Fanego R.Comparison of major immunoglobulins intrathecal synthesis patterns in Ecuadorian and Cuban patients with angiostrongyliasis. Am J Trop Med Hyg 2011; 84(3):406-10
Dos casos de meningitis crónica por Angiostrongylus cantonensis.Réplica. Rev Neurol. 2011 1;52(7):448. Sabina-Molina D, Dorta-Contreras AJ, Padilla-Docal B, Bu-Coifiu Fanego R.
Dorta-Contreras AJ , Padilla-Docal B, Moreira JM, Martini Robles L, Muzzio Aroca J, Alarcón F et al.Neuroimmunological findings in Angiostrongylus cantonensis meningitis in Ecuadorian patients. Arq. Neuropsiquiatr 2011; 69(3) 466-469.
Mannose-binding lectin deficiency with eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in children: a case series.J Med Case Reports 2011, 5:330 Bárbara Padilla-Docal, Alberto J Dorta-Contreras, Raisa Bu-Coifiu-Fanego, Rene Martinez-Alderete, Olga Susana De Paula-Almeida, Hansotto Reiber, Jens Christian Jensenius.
Different intrathecal immunoglobulins synthesis patterns in human host indicate different strains of Angiostrongylus cantonensis. Med Hypotheses. 2012 Jun 8. [Epub ahead of print];79: 311-12 Padilla-Docal B, Dorta-Contreras AJ.	2012
Intrathecal Activation as a Typical Immune Response within the Central Nervous System in Angiostrongyliasis Am. J. Trop. Med. Hyg.2013; 88(2); 230-235.Barbara Padilla-Docal, Ivonne Iglesias-Gonzalez, Raisa Bu-Coifiu-Fanego,Carmen Aleida Socarras-Hernandez, and Alberto Juan Dorta-Contreras.	2013
Sabina-Molina Domingo, Padilla-Docal Bárbara, Bu-Coifiu-Fanego Raisa, Dorta-Contreras Alberto Juan. Meningitis crónica por Angiostrongylus Cantonensis. Rev. Ecuat. Neurol 2013;22 (1-3):117-122
Meningoencefalitis eosinofílica por Angiostrongylus cantonensis y variables meteorológicas. Revista Habanera de Ciencias Médicas [revista en Internet]. 2015 [citado año mes dia]; 0(5):[aprox. 10 p.]. Disponible en: http://www.revhabanera.sld.cu/index.php/rhab/article/view/780.Dorta-Contreras A, Ramos-Plasencia A, Padilla-Docal B, Bú-Coifiu-Fanego R, Iglesias I	2015
Junco-Rodríguez J, Cárdenas-de-Baños L, Pacheco-Mendoza J, Dorta-Contreras A. Producción científica cubana sobre Angiostrongylus cantonensis. 1981-2015. Revista Habanera de Ciencias Médicas [revista en Internet]. 2016 [citado 2016 Jul 29]; 15(4): 610-629 Disponible en: http://www.revhabanera.sld.cu/index.php/rhab/article/view/1048	2016
Martini Robles, Dorta Contreras AJ, editores. Angiostrongylus cantonensis. Emergencia en América. La Habana: Academia; 2016.p.7-17. ISBN 978-959-270-368-1.
Dorta-Contreras AJ , Martini-Robles L, Iglesias González IM, Martínez-Larrarte JP, Castillo-González W, González-Losada C, Jensenius JC, Reiber H. Recent neuroimmunological findings in Eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. En: Proceedings of the IV Symposium of Tropical Health/COST Action CM 1307 (WG3 and WG4) Joint Meeting. Priorities in Tropical Health and parasite-borne disease: new drugs with new targets, and how to deliver them. Servicio de Publicaciones. University of Navarra, Pamplona, 2017. P.35. [ISBN: 978-84-8081-556-7] Disponible en http://www.simposiosaludtropical.com/	2017
Dorta-Contreras AJ, Martini-Robles L, Iglesias González IM, Martínez-Larrarte JP, Castillo-González W, González-Losada C, Jensenius JC, Reiber H. Angiostrongylus cantonensis. Emergencia en América. En: Proceedings of the IV Symposium of Tropical Health/COST Action CM 1307 (WG3 and WG4) Joint Meeting. Priorities in Tropical Health and parasite-borne disease: new drugs with new targets, and how to deliver them. Servicio de Publicaciones.
Dorta-Contreras A. Deficiencia de manosa unida a lectina (MBL) en niños con meningoencefalitis por Angiostrongylus cantonensis. Una serie de casos. Revista Cubana de Hematología, Inmunología y Hemoterapia [revista en Internet]. [citado 2018 Ago 1];33(S1):[aprox. 4 p.]. Disponible en: http://www.revhematologia.sld.cu/index.php/hih/article/view/799
González-Losada C, Padrón-González AA, Lumpuy-Castillo J, Rodriguez-Pérez A, Castillo-González W, Dorta-Contreras AJ. Intrathecal Activation of the Lectin Pathway in Patients with Eosinophilic Meningitis by Angiostrongylus cantonensis. FASEB J 2018; 32, 1_supplement: 741.2. Disponible en: https://www.fasebj.org/toc/fasebj/32/1_supplement , Abstract 741.2 ;Consultado Abril 22, 2018.	2018

REFERENCES

1 - Dorta Contreras AJ, Reiber H. Intrathecal synthesis of immunoglobulins in eosinophilic meningoencephalitis due to Angiostrongylus cantonensis. Clin Diagn Lab Immunol 1998;5:452-455.

2 - Padilla-Docal B, Dorta-Contreras AJ, Bu-Coifiu-Fanego R, Fundora-Hernandez H, Callol-Barroso J, Sanchez-Martinez C. Intrathecal synthesis of IgE in children with eosinophilic meningoencephalitiscaused by Angiostrongylus cantonensis.Cerebrospinal Fluid Res. 2008;5(1):18 disponible en: http://www.cerebrospinalfluidresearch.com/content/5/1/18 .

3 - Padilla-Docal B, Dorta-Contreras AJ, Bu-Coifiu-Fanego R. Activación y biosíntesis intratecal de C3c en niños con meningoencefalitis eosinofílica por Angiostrongylus cantonensis.Rev Neurol. 2009;48:632-5.

4 - Padilla-Docal B, Dorta-Contreras AJ, Bu-Coifiu-Fanego R, Rodríguez-Rey A, Gutiérrez-Hernández JC, de Paula-Almeida SO. Reibergram of intrathecal synthesis of C4 in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis. Am J Trop Med Hyg 2010; 82(6):1094-8.

5 - Padilla-Docal B, Iglesias-Gonzalez I, Bu-Coifiu-Fanego R, Socarras-Hernandez CA, Dorta-Contreras AJ. Intrathecal. Activation as a Typical Immune Response within the Central Nervous System in Angiostrongyliasis Am. J. Trop. Med. Hyg.2013;88(2);230-235.

6 - Dorta-Contreras A. Deficiencia de manosa unida a lectina (MBL) en niños con meningoencefalitis por Angiostrongylus cantonensis. Una serie de casos. Revista Cubana de Hematología, Inmunología y Hemoterapia [revista en Internet]. [citado 2018 Ago 1];33(S1):[aprox. 4 p.]. Disponible en: http://www.revhematologia.sld.cu/index.php/hih/article/view/799 .

7 - González-Losada C, Padrón-González AA, Lumpuy-Castillo J, Rodriguez-Pérez A, Castillo-González W, Dorta-Contreras AJ. Intrathecal Activation of the Lectin Pathway in Patients with Eosinophilic Meningitis by Angiostrongylus cantonensis. FASEB J 2018;32, 1_supplement: 741.2. Disponible en: https://www.fasebj.org/toc/fasebj/32/1_supplement , Abstract 741.2 ;Consultado Abril 22, 2018.

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