Frequency and phenotype alterations in monocyte subsets from dengue patients
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1
Universidad de Antioquia, Instituto de Investigaciones Médicas, Facultad de Medicina, Colombia
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2
Universidad de Antioquia, Departamento de Microbiología y Parasitología, Facultad de Medicina, Colombia
Introduction
Dengue is an infectious disease with a high incidence in tropical and subtropical regions worldwide. It is caused by a virus named also as dengue, transmitted by vectors of the Aedes genus. This disease mainly courses with febrile stages, myalgia and articular pain, which is auto-resolved in the most of cases. However, 5 to 10% of the patients develop severity manifestations, characterized by vascular leakage, hemorrhages, organic dysfunction and in many cases, death. At the moment, the reasons whereby some patients present severe dengue are unknown. Nevertheless, it has been proposed that monocytes and their products must participate in this process. Monocytes are both target of dengue virus infection and participate in the viremia resolution; however, taking in account that each monocyte subset has different functions, it is incompletely known whether they have contrasting roles in the immunopathology of this disease, or whether they have phenotypic alterations with the in vivo infection.
Monocytes can be divided in three subsets based on the lipopolysaccharide receptor CD14 and the Fc receptor CD16 expression, in classical (CD14++CD16-), intermediate (CD14++CD16+) and non-classical (CD14+CD16++). Whether there are phenotypic alterations in monocyte subsets associated with severe manifestations of this disease, these could be proposed as biomarkers for the prognosis of dengue patients. Hence, in this work the frequency, absolute number and phenotype of the monocyte subsets in dengue patients were evaluated.
Methodology
Peripheral blood samples from dengue patients and healthy controls were collected. Patients included those with clinical manifestations related to dengue and positive to a rapid test for NS1 antigen, and IgM and IgG specific for the virus. A flow cytometry was performed to evaluate the expression of CD64, CD86, CD11b, CD54, CD18 and CX3CR1 in each monocyte subset, according to the CD14 and CD16 expression on HLA-DR positive cells. Statistical comparisons between the study groups were made with the non-parametric Mann Whitney test.
Results
There was an increased frequency of intermediate monocytes and a significant decrease in the non-classical subset in dengue patients. An augmented expression of the αM integrin CD11b and Fc receptor CD64, without changes in the β2 integrin CD18 was observed in the three subsets of monocytes from patients. An increase in the expression of the intercellular adhesion molecule 1 CD54 and a decrease in fractalkine receptor CX3CR1 was observed both, in non-classical and intermediate monocyte subsets from dengue patients. On the other hand, the expression of CD86 was higher on non-classical subset from patients compared to healthy controls.
Conclusions
The monocyte subpopulation most affected in dengue patients was the non-classical. Also, this subset was significantly reduced, had an increase of CD11b and CD64 expression, which are associated with high susceptibility to the infection and antibody dependent enhancement in dengue infection, respectively.
The CX3CR1 expression on CD16+ monocytes has been previously associated with their interaction with the endothelium. Therefore, the increases in the expression of CD54 and CD86 in non-classical monocytes, together with the decreased expression of CX3CR1, suggest these cells could be activated in dengue patients and being recruited to the marginal zone of blood vessels, possible contributing to the develop of hemorrhagic manifestations observed in these patients.
Acknowledgements
The authors are grateful to the grants “Sostenibilidad 2015-2016 and Sistema Universitario de Investigaciones" from Universidad de Antioquia, and to COLCIENCIAS (111556933247).
Keywords:
Dengue,
Monocytes,
CD14,
CD16,
denv,
Virus Diseases
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:
Naranjo-Gomez
JS,
Castillo
JA,
Velilla
PA,
Rojas
M and
Castano
D
(2015). Frequency and phenotype alterations in monocyte subsets from dengue patients.
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.2015.05.00180
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Received:
22 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
Prof. Diana Castano, Universidad de Antioquia, Instituto de Investigaciones Médicas, Facultad de Medicina, Medellin, Colombia, dmcastano@gmail.com