Figure 2.

Potential mechanisms for immune mediated enhancement of DENV infection. A) Immune responses following primary DENV infection include infection of monocytes and other antigen presenting cells which produce cytokines/chemokines and present antigen to lymphocytes. Type-specific and cross-reactive B and T lymphocytes are activated. B lymphocytes produce serotype-specific, neutralizing antibodies as well as cross-reactive, weakly or non-neutralizing antibodies. B) Following secondary heterologous infection, uptake of DENV is facilitated through binding of cross-reactive, non-neutralizing antibodies from a previous infection (or maternally derived antibodies in the case of primary infection in infants). Additionally, there is activation of cross-reactive T cells that produce skewed cytokine responses and demonstrate decreased cytotoxicity for DENV infected cells. Massive quantities of pro-inflammatory cytokines (“cytokine storm”) result in increased vascular permeability and plasma leakage. Furthermore, expression or release of DENV-NS1 by infected cells may mediate complement activation resulting in increased vascular permeability.