TNF is a potent proinfl ammatory cytokine produced early in the innate immune response to infection that promotes a wide range of immunologic responses. Excessive systemic TNF is responsible for many symptoms of clinical infection and may lead to fatal complications. Studies have demonstrated a signifi cant genetic contribution to circulating TNF levels, with 50%-60% of variance in TNF levels genetically determined (19) (20) (21) . The most studied SNP is at position −308 (rs1800629), with the A allele associated with 20%-40% greater TNF production (22) (23) (24) and with susceptibility to and severity of numerous infectious diseases (20, 22, 25, 26) . Carriage of the A allele at the −238 position (rs361525) also has been associated with a variety of diseases (20, 22) . MBL, another key component of the innate immune system, is a soluble protein of the collectin family that binds to microbial surfaces and promotes phago-opsonization directly and indirectly by activating the lectin complement pathway. Low serum MBL levels are common and associated with an increased risk for a variety of infections and autoimmune diseases (15, (27) (28) (29) , including acute respiratory infection in young children (12) . MBL levels are strongly infl uenced by genetic factors, with >75% of variation in MBL levels explained by a small number of polymorphisms in the MBL2 gene (30) . Variant proteins are unstable and of lower oligomeric form, which decreases affi nity for microbial ligands and complement-activating ability. Each variant produces signifi cantly reduced serum MBL levels.