Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection

Abstract

IntroductionZika virus (ZIKV) and dengue virus (DENV) co‐circulated during latest outbreaks in Brazil, hence, it is important to evaluate the host cross‐reactive immune responses to these viruses. So far, little is known about human T cell responses to ZIKV and no reports detail adaptive immune responses during DENV/ZIKV coinfection.MethodsHere, we studied T cells responses in well‐characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV‐exposed healthy donors. We evaluated chemokine receptors expression and single/multifunctional frequencies of IFNγ, TNF, and IL2‐producing T cells during these infections. Even without antigenic stimulation, it was possible to detect chemokine receptors and IFNγ, TNF, and IL2‐producing T cells from all individuals by flow cytometry. Additionally, PBMCs’ IFNγ response to DENV NS1 protein and to polyclonal stimuli was evaluated by ELISPOT.ResultsDENV and ZIKV infections and DENV/ZIKV coinfections similarly induced expression of CCR5, CX3CR1, and CXCR3 on CD4 and CD8 T cells. DENV/ZIKV coinfection decreased the ability of CD4+ T cells to produce IFNγ+, TNF+, TNF + IFNγ+, and TNF + IL2+, compared to DENV and ZIKV infections. A higher magnitude of IFNγ response to DENV NS1 was found in donors with a history of dengue infection, however, a hyporesponsiveness was found in acute DENV, ZIKV, or DENV/ZIKV infected patients, even previously infected with DENV.ConclusionTherefore, we emphasize the potential impact of coinfection on the immune response from human hosts, mainly in areas where DENV and ZIKV cocirculate.

T‐cells producing multiple combinations of IFNγ, TNF and IL10 are associated with mild forms of dengue infection

“…Dengue virus‐specific T‐cells producing IFNγ and TNF can be found in human 9,29–31,37 and experimental 40 dengue infection. Interestingly, IFNγ + TNF + CD8 + T‐cells were also found to be increased in patients with a history of Hemorrhagic Dengue, 9 suggesting a deleterious role of these cells.…”

“…There is little information about multifunctional T‐cells in dengue infection, 29–31 especially with regard to IL10 + Th1 and IL10 + Tc1 cells. In this work, we aimed to investigate the presence of these cells in different clinical forms of dengue infection.…”

Detection of Zika virus in paired urine and amniotic fluid samples from symptomatic and asymptomatic women and their babies during a disease outbreak: association with neurological symptoms in newborns

“…There is a hypothesis that the simultaneous presence of more than one flavivirus infection may potentiate negative sequelae. However, these studies are not definitive and need further exploration (Badolato-Correa et al 2018). Even in animal models, the results are still inclusive (Langerak et al 2019).…”

Cocirculation and Coinfection Associated to Zika Virus in the Americas

“…Currently, one of the major public health and biomedical challenges for the region is represented by cocirculation and coinfection of different flaviviral and nonflaviviral arboviruses [1,[5][6][7][8][9]. Their differentiation as their cross-reactivity between flaviviruses, particularly, implies immunological and diagnostic problems, when used serological tests [10][11][12][13].…”

“…In 2015, ZIKV emerged in LAC (although circulated apparently since 2013 in a silent pattern) as a leading public health priority, approximately 2 years after the CHIKV epidemic, leading to ZIKV, CHIKV, and DENV cocirculation, and the reporting of coinfections in different combinations. Although in the case of ZIKV infection, 80% of cases could be asymptomatic, clinical diagnosis of ZIKV, CHIKV, and DENV remains a challenge due to the considerable overlap in clinical presentations between them, and with other viral and nonviral infections [1,4,5], in addition also the problem of infection in patients with existing comorbidities that can lead to atypical, severe, and even fatal cases.…”