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Babesia bovis: lipids from virulent S2P and attenuated R1A strains trigger differential signalling and inflammatory responses in bovine macrophages

Published online by Cambridge University Press:  03 January 2013

G. GIMENEZ ,
M. L. BELAUNZARÁN ,
C. V. PONCINI ,
F. C. BLANCO ,
I. ECHAIDE ,
P. I. ZAMORANO ,
E. M. LAMMEL ,
S. M. GONZÁLEZ CAPPA  and
E. L. D. ISOLA
G. GIMENEZ*
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
M. L. BELAUNZARÁN
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
C. V. PONCINI
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
F. C. BLANCO
Affiliation:
Instituto de Biotecnología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, INTA-Castelar, Nicolas Repetto y de los Reseros s/n, 1686 Hurlingham, Buenos Aires, Argentina
I. ECHAIDE
Affiliation:
Instituto Nacional de Tecnología Agropecuaria (INTA), Estación Experimental Agropecuaria Rafaela, Ruta 34 km 227, 2300 Santa Fe, Argentina
P. I. ZAMORANO
Affiliation:
Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, INTA-Castelar, Nicolas Repetto y de los Reseros s/n, 1686 Hurlingham, Buenos Aires, Argentina
E. M. LAMMEL
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
S. M. GONZÁLEZ CAPPA
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
E. L. D. ISOLA
Affiliation:
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina
*
*Corresponding author: Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA-CONICET). Facultad de Medicina, Paraguay 2155 piso 13, C1121ABG Buenos Aires, Argentina. Tel: +54 11 5950 9500 ext. 2191. Fax: +54 11 5950 9577. E-mail: paradife@fmed.uba.ar
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Summary

The intra-erythrocytic protozoan Babesia bovis is an economically important pathogen that causes an acute and often fatal infection in adult cattle. Babesiosis limitation depends on the early activation of macrophages, essential cells of the host innate immunity, which can generate an inflammatory response mediated by cytokines and nitric oxide (NO). Herein, we demonstrate in bovine macrophages that lipids from B. bovis attenuated R1A strain (LA) produced a stronger NO release, an early TNFα mRNA induction and 2-fold higher IL-12p35 mRNA levels compared to the lipids of virulent S2P strain (LV). Neither LA nor LV induced anti-inflammatory IL-10. Regarding signalling pathways, we here report that LA induced a significant phosphorylation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2) whereas LV only induced a reduced activation of ERK1/2. Besides, NF-κB was activated by LA and LV, but LA produced an early degradation of the inhibitor IκB. Interestingly, LV and the majority of its lipid fractions, exerted a significant inhibition of concanavalin A-induced peripheral blood mononuclear cell proliferation with respect to LA and its corresponding lipid fractions. In addition, we determined that animals infected with R1A developed a higher increase in IgM anti-phosphatidylcholine than those inoculated with S2P. Collectively, S2P lipids generated a decreased inflammatory response contributing to the evasion of innate immunity. Moreover, since R1A lipids induced a pro-inflammatory profile, we propose these molecules as good candidates for immunoprophylactic strategies against babesiosis.

Keywords

LipidsBabesia bovisbovine macrophagessignallinginnate immunityanti-phospholipid antibodies
Type
Research Article
Information
Parasitology , Volume 140 , Issue 4 , April 2013 , pp. 530 - 540
Copyright
Copyright © Cambridge University Press 2013

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