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. An understanding of immunologic responses to Ot infection, particularly immunity after infection, has remained a major gap of knowledge in the field. While it is known that anti-Ot IgG in infected humans seems to be short-lived, recent studies have reported autoreactive IgM antibodies in scrub typhus patients, including antibodies reactive against nuclear components, DNA, and platelets. Yet, mechanistic studies of B cell responses in the secondary lymphoid organs of human patients are severely lacking. This article highlights feasible methods to investigate important aspects of humoral immunity and details avenues to obtain samples from post-mortem and ante-mortem Ot-infected patients. A pioneer study identified the antibodies were protective against homologous Ot challenge. Comparative studies for the humoral immune responses to Ot Karp versus Gilliam strains have revealed the impairment of B cell and germinal center responses during severe, but not self-limiting infection in C57BL/6 mice. Further studies are needed, particularly in scrub typhus patients, to help understand and define deficiencies in the acute B cell response and long-lived humoral immunity.