Our study demonstrates that RasGRP3, a regulator of both Ras and Rap1, negatively regulates the production of proinflammatory cytokines (especially IL-6) by activating Rap1 and inhibiting ERK1/2 activation in response to low levels of TLR agonists, which may serve as an early regulatory machinery to limit inflammatory response of macrophages to feeble infection. The gene discussed is MAPK3; the disease is infection.