TLR4 and bacterial infectious disease with sepsis: The most dramatic phenotype was reported in the original publication by Malley et al. (Malley et al., 2003; Srivastava et al., 2005), showing that C3H/HeJ mice, which carry a loss-of-function tlr4 mutation, are more susceptible to pneumococcal colonization after nasopharyngeal challenge, eventually resulting in invasive infection, bacteremia and death.