These findings suggest the presence in the CFS > 3kDa fraction of high molecular weight components and/or cell wall fragments able to directly interact with host cell receptors (e.g. TLR-2, TLR-4) leading to a stimulatory response which is masked by ≤ 3kDa components in unfractionated CFS. Here, TLR4 is linked to myalgic encephalomeyelitis/chronic fatigue syndrome.