Proposed scheme of the first encounter between B. pseudomallei and the immune system. Putative virulence factors on the bacterial cell surface include lipopolysaccharide (LPS), capsular polysaccharides and flagella. There might also be a role for biofilm formation. Bacterial gene regulation through N-acyl-homoserine lactones (AHLs) could be crucial for bacterial survival in vivo. Type III secretion systems (TTSSs) might facilitate invasion of the bacterium into the host cell, and enable escape from endocytic host-cell vesicles. Monocytes are probably the most important immune cells in early infection. Based on evidence from other Gram-negative pathogens, there might be a role for the Toll-like receptors (TLRs). TLR4, with its co-receptors MD2 and CD14, might recognize B. pseudomallei LPS, whereas TLR5 might recognize flagella, although to date there are no published data to support this. The complement receptors CR1, CR3 and possibly FcgammaR mediate opsonin-dependent phagocytosis. Recognition of B. pseudomallei will cause activation of pro-inflammatory genes through nuclear factor (NF)-kappaB and lead to the activation of the immune response through the release of pro-inflammatory cytokines.