Humoral Immune Response to Orientia tsutsugamushi Infection: Recent Research Findings and Future Studies

Orientia tsutsugamushi (Ot), an intracellular bacterium in the family Rickettsiaceae, is the etiological agent of scrub typhus. Understanding of the immunologic responses to Ot infection, particularly immunity after infection, has remained a major knowledge gap. Although anti-Ot IgG appears to be short-lived in infected humans, recent studies have reported autoreactive IgM antibodies in people with scrub typhus, including antibodies reactive to nuclear components, DNA, and platelets. However, mechanistic studies of B cell responses in the secondary lymphoid organs of infected humans are severely lacking. This article highlights feasible methods to investigate important aspects of humoral immunity, and avenues to obtain samples from post-mortem and ante-mortem Ot-infected people. A pioneer study identified that serum passive transfer could protect against homologous Ot challenge. Studies comparing humoral immune responses to Ot Karp versus Gilliam strains have revealed impaired B cell and germinal center (GC) responses during severe, but not self-limiting, infection in C57BL/6 mice. Further studies are needed, particularly in people with scrub typhus, to help understand and define deficiencies in the acute B cell response and long-lived humoral immunity.