The clinico-pathophysiological responses observed in rhesus macaques after ID O. tsutsugamushi inoculation demonstrated striking similarity to human disease, with development of fever during bacteremia, marked eschar formation, regional followed by generalized lymphadenopathy, similar bacteremia onset and duration, altered liver function, increased WBC counts, and pathogen-specific antibody (IgM and IgG) and cell-mediated immune responses. Here, CD40LG is linked to Lymphadenopathy.