Splenic architecture disruption and parasite-induced splenocyte activation and anergy in Plasmodium falciparum-infected Saimiri sciureus monkeys

Malaria Journal

Research

José APC Muniz¹  Marco A Krieger²  Marcelo Pelajo-Machado³  Paulo RR Totino⁴  Mariana T Souza⁴  Cláudio Tadeu Daniel-Ribeiro⁴  Leonardo JM Carvalho⁴  Francisco A Alves⁵  Maria Paula C Schneider⁶  Evonnildo C Gonçalves⁷  Marcia CR Andrade⁸ 

[1] Centro Nacional de Primatas (Cenp), SVS, Belém, Brazil;Instituto Carlos Chagas de Biologia Molecular, Curitiba, Brazil;Laboratório de Patologia, Instituto Oswaldo Cruz (IOC), Fiocruz, Rio de Janeiro, Brazil;Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fiocruz, Rio de Janeiro, Brazil;Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fiocruz, Rio de Janeiro, Brazil;Laboratório de Imunobiologia, Universidade Federal do Pará (UFPA), Belém, Brazil;Laboratório de Polimorfismo de DNA, Universidade Federal do Pará (UFPA), Belém, Brazil;Laboratório de Tecnologia Biomolecular, Universidade Federal do Pará (UFPA), Belém, Brazil;Serviço de Criação de Primatas Não-Humanos, CECAL-Fiocruz, Rio de Janeiro, Brazil;

关键词: Malaria;    Saimiri;    Aotus;    Plasmodium falciparum;    Cytokines;    Spleen;   

DOI  :  10.1186/s12936-015-0641-3

 received in 2014-10-24, accepted in 2015-03-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe understanding of the mechanisms of immunity in malaria is crucial for the rational development of interventions such as vaccines. During blood stage infection, the spleen is considered to play critical roles in both immunity and immunopathology of Plasmodium falciparum infections.MethodsSaimiri sciureus monkeys were inoculated with blood stages of P. falciparum (FUP strain) and spleens removed during acute disease (days 7 and 13 of infection) and during convalescence (15 days after start of chloroquine treatment). Cytokine (IFNγ, TNFα, IL2, IL6, IL10, and IL12) responses of splenocytes stimulated with P. falciparum-parasitized red blood cells were assessed by real-time PCR using specific Saimiri primers, and histological changes were evaluated using haematoxylin-eosin and Giemsa-stained slides.ResultsEarly during infection (day 7, 1-2% parasitaemia), spleens showed disruption of germinal centre architecture with heavy B-cell activation (centroblasts), and splenocytes showed increased expression of IFNγ, IL6 and IL12 upon in vitro stimuli by P. falciparum-parasitized red blood cells (pRBC). Conversely, 15 days after treatment of blood stage infection with chloroquine, splenocytes showed spontaneous in vitro expression of TNFα, IL2, IL6, IL10, and IL12, but not IFNγ, and stimulation with P. falciparum pRBC blocked the expression of all these cytokines. During the acute phase of infection, splenic disarray with disorganized germinal centres was observed. During convalescence, spleens of the chloroquine-treated animals showed white pulp hyperplasia with extensive lymphocyte activation and persistency of heavily haemozoin-laden macrophages throughout the red pulp.ConclusionsInability to eliminate haemozoin is likely involved in the persistent lymphocyte activation and in the anergic responses of Saimiri splenocytes to P. falciparum pRBC, with important negative impact in immune responses and implications for the design of malaria vaccine.

【 授权许可】

Unknown   
© Alves et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.