Characterization of lymphocyte subsets and cytokine patterns in coinfected patients with dengue and HIV
-
1
Fundação Oswaldo Cruz - RJ, Instituto Oswaldo Cruz - FIOCRUZ, Brazil
-
2
Instituto Oswaldo Cruz - FIOCRUZ, Instituto de Pesquisa clínica Evandro Chagas (IPEC), Brazil
-
3
Universidade Federal do Mato Grosso do Sul, Departamento de Clínica Médica, Brazil
-
4
Hospital Universitário Gafreé-Guinle, Universidade Federal do Estado do Rio de Janeiro, Brazil
Background: Dengue is known as the most important arboviruses in the world presented no treatment. Currently, approximately 40 million people are infected with the human immunodeficiency virus (HIV). Many of these individuals fail to control viral replication and thus progressing to Acquired Immunodeficiency Syndrome (AIDS), otherwise treated. In this context, HIV infection is a major public health problem, as well as dengue. As in dengue infection, dysregulation of apoptosis and activation mechanisms are seen as important factors in the depletion of CD4 and CD8 T cells and disease progression during HIV infection. Little is known about the immunological mechanisms that could explain the mildest form of dengue in DENV and HIV (DENV/HIV) coinfected patients. Objective: We aim to investigate the selective functional role of different lymphocytes subsets in the clinical manifestations, viral load, activation, and cell death during coinfection with DENV and HIV in order to understand the mechanisms involved in susceptibility to severity of both diseases. Material and methodology: The study population was carried out in Brazil from 2008 to 2011 during DENV-1 and 2 outbreaks. The Dengue patients were classified according to the parameters established for the WHO in 2009. Immunologic assessments by specific activation/death markers and multiple labeling of PBMCs were performed for flow cytometry analysis. The circulating levels of cytokines were quantified in the plasma samples from patients with DENV monoinfection (n=71), DENV/HIV coinfection (n=21), HIV monoinfection (15) and samples from healthy donors (n=10) by ELISA or Multiplex immunoassay kits. The nonparametrict Mann–Whitney U-test was used to compare cytokine levels, lymphocytes subsets data in the patients groups classified as mono or coinfected with DENV and/or HIV. Results: For the first time we observed that patients coinfected with DENV and HIV had lower frequency of CD4 T lymphocytes, even those presenting undetectable HIV viral load and making use of some kind of anti-retrovirus therapy. We speculate that this phenomenon may be due to factors associated with infection by dengue. It is known that a substantial activation is inversely proportional to the levels of CD4 T cells in HIV and also dengue infections, suggesting that activation may also contribute to the depletion of these cells. Furthermore, we showed a significant high frequency of CD4 T expressing CCR5 together with a positive correlation between both T CCR5+ subsets and a cytotoxic phenotype in patients coinfected suggesting an important role in homing of these cells expressing a co-receptor for HIV to inflammatory compartments. Our data also shown that DENV infection induced increase of T cells frequency expressing the death receptor Fas/CD95 concomitantly with a decrease of cells expressing low levels of Bcl-2. Despite T-cell activation and apoptosis were increased in DENV and HIV infection, none of these indices was affected by coinfection even in HIV patients receiving antiretroviral treatment. Finally, we observed a significant increase of soluble chemokine IL-8 and a tendency to a decrease of IP-10, pro-inflammatory and regulatory cytokines plasma levels in patients coinfected DENV / HIV which could probably due to a low DENV viremia and / or HAART with consequent reduction of local inflammation and mild evolution of dengue disease. Conclusions: We can conclude that our study corroborates with previous data in which most HIV patients which presented the DENV infection did not progress to a more severe clinical scenario comparing the DENV monoinfected patients. Exacerbation of T lymphocyte effectors responses could be one of the multiple factors associated with susceptibility to dengue severity. However, the hallmark of HIV infection is the gradual weakening of the immune system. Such aspects may explain in part the lower incidence of dengue severe cases in coinfected patients. We suggest that the association between activation and apoptosis phenomena, as well as the immunosuppressive state observed in HIV+ patients treated, could be potentiated in coinfected patients and having a striking effect on dengue progression.
The authors have declared that no competing interests exist.
Acknowledgements
We would like to acknowledge Ana Rita Motta Castro and her students, for their assistance with patient recruitment and sample collection. We also would like to thank Alessandro Marins dos Santos and Daniela Beghini for the help in the FACS CyAn facility. We are indebted to the Flavivirus Laboratory team led by Dr. Rita Nogueira at FIOCRUZ, RJ and Plínio Barcelar Laboratory in Campos de Goytacazes for laboratory diagnosis.
Keywords:
Dengue,
HIV,
Apoptosis,
Activation markers,
Lymphocytes
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Infectious and parasitic diseases
Citation:
Torrentes-Carvalho
A,
Marinho
CF,
Pinto
LM,
Hottz
ED,
Da Silva
JB,
Cunha
RV,
Damasco
PV,
Kubelka
CF and
Azeredo
EL
(2015). Characterization of lymphocyte subsets and cytokine patterns in coinfected patients with dengue and HIV.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00169
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
15 Apr 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
Dr. Amanda Torrentes-Carvalho, Fundação Oswaldo Cruz - RJ, Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Rio de Janeiro, 21040-360, Brazil, biotorrentes@gmail.com