Environmental influences on antibody-enhanced dengue disease outcomes

Daniel Guerreiro Diniz, César Augusto Raiol Fôro, Maíra C Pereira Turiel, Marcia CK Sosthenes, Sâmia Demachki, Giovanni Freitas Gomes, Carla M Damasceno Rego, Marina Cutrim Magalhães, Brunno Gomes Pinho, Juliana Pastana Ramos, Samir M Moraes Casseb, Maysa de Vasconcelos Brito (+7 others)
2012 Memórias do Instituto Oswaldo Cruz  
Clinical and pathological evidence implicating abnormal cytokine release as the main mediator of disease and an increased risk of severe dengue disease have been described during secondary dengue virus (DENV) infections (Kurane & Ennis 1992) . Indeed elevated levels of tumour necrosis factor (TNF)-α have been detected in dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) patients (Vitarana et al. 1991 , Hober et al. 1993 , Nguyen et al. 2004 ) and the production of this cytokine was
more » ... lated with increased numbers of macrophages/monocytes (de-Oliveira-Pinto et al. 2012), which are potent phagocytic cells and primary targets for DENV infection (Kang-wanpong et al. 1995 , Jessie et al. 2004 ). These cells express all three classes of FCγR making them especially prone to DENV entry in the form of virus-antibody immune complexes (Mathew & Rothman 2008). In addition, recent studies have demonstrated that DENV-specific memory Tcells from a prior infection respond to heterologous DENV serotypes with an altered cytokine profile and that the level of activation and expansion of these memory cells during acute DENV infection correlates with the disease severity (Rothman 2010). In addition, significant cross reactivity between DENV serotypes was shown in CD8(+) T-cells after a naturally acquired primary infection with differential T-cell receptor signalling after stimulation with homologous and heterologous peptides (Friberg et al. 2011) . DENV entry is facilitated by the phagocytosis of immune complexes via Fc receptors on monocytes (Daughaday et al. 1981 ) and studies of immune responses have reported circulating immune complexes and complement activation during the fever-to-defervescence period in which haemorrhage, plasma leakage and/or circulatory failure occur in patients with DHF and/or OSS (Ruangjirachuporn et al. 1979 , Wang et al. 2006) . In endemic areas, where DHF incidence remains high, mosquito vectors are abundant and multiple in-
doi:10.1590/s0074-02762012000800010 pmid:23295753 fatcat:i4wj7f3n4vgh5olh7ahhtyc5xe