Abstract
Various mouse models to study dengue have been described by different authors, some of them using immunodeficient or some using humanized mice. Our group reported previously a deadly murine model, which used the intracranial inoculum of highly virulent Dengue virus (DENV) in immune competent mouse. Here we present a model of immune competent mouse (C57BL/6), infected subcutaneously by the same highly virulent DENV (DENV3 genotype I). In this immunocompetent systemic mice model, the cytokine levels and hematological parameters such as total and differential leukocyte and platelets counts, together with weight loss, were considered important monitoring parameters, allowing a better understanding of the systemic human disease. Mice were inoculated subcutaneously and evaluated by the percentage weight variation as well as the clinical signs. Hematological parameters and cytokines levels were measured and viral titration in brain tissue or serum neutralization was performed to confirm mice infection. The subcutaneously DENV inoculated mice showed weight loss after infection, but they did not show any other clinical signs. The leukocytes and platelets decreased after subcutaneous inoculation. The cytokines TNF alpha and IFN gamma increased after infection in mice. The subcutaneous model provided scope for improved understanding of the dengue pathogenesis, as well as possible mechanism for protection to subsequent mouse infected by intracranial route in mice. This model could be used to study the vertebrate immune response and evaluation of drugs or vaccine against dengue virus.
Highlights
Dengue, one of the most prevalent infectious diseases in the 21st century [1], is a mosquito-borne viral disease
The same highly virulent Dengue virus (DENV) and the same strain of mice used in previous studies but inoculated subcutaneously (SC)
We showed in our model, that TNF alpha in the spleen and IFN gamma in the liver of immune competent mice 6 hours after infection with DENV have increased (Figure 5(a) and Figure 5(d), respectively), showing the importance of these cytokines to the host defense against a highly virulent dengue virus inoculated by via subcutaneous
Summary
One of the most prevalent infectious diseases in the 21st century [1], is a mosquito-borne viral disease. The uses of hematological parameters such as differentiation and counting of total leukocytes, red blood cells, platelets, lymphocytes, neutrophils and monocytes [10] [11] [12] [13] are important disease markers, allowing a better understanding of dengue disease and its response mechanisms in the body of the animals studied [5] [14] [15] [16] [17] Cytokines such as IFN gamma, TNF alpha and IL12p70 are used to evaluate the immune response to DENV infection [18] [19] [20]
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