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A critical aspect of the macrophage inflammatory response to pathogen challenge is the rapid production of TNF that signals in autocrine and paracrine manners to carry out innate and adaptive immune responses. Toll-Like Receptors (TLRs) are highly expressed in macrophages, and recognize extracellular and intracellular pathogen signals leading to the activation of transcription factors and cytokine production. There have been numerous TLR-mediated signaling mechanisms identified that control the production of TNF, but it remains unclear how they coordinate together in macrophages.