Immunosuppression associated with the development of chronic infections with Rickettsia tsutsugamushi: adherent suppressor cell activity and macrophage activation

Abstract

Measures of general immunocompetency such as lymphocyte responses to mitogens and alloantigens and the ability to produce antibody to T-dependent and T-independent antigens were evaluated during the development of chronic infections with Rickettsia tsutsugamushi resulting from subcutaneous infection of BALB/c mice. It was found that a transient immunosuppression was demonstrable regardless of the infecting strain of rickettsiae; however, the immunosuppression produced by the Karp and Kato strains was more pronounced and longer lived. As a marked splenomegaly resulting from inflammatory macrophage influx accompanied this immunosuppression, mitogenand antigen-induced lymphocyte proliferation was also evaluated after adherent cell depletion or in the presence of indomethacin, and both treatments significantly improved the responses. Isolated splenic macrophages were shown to suppress the responses of lymphocytes from naive mice as well as to exhibit parameters of activation including tumor cell cytolysis and cytostasis and the ability to inhibit the replication of R. tsutsugamushi in vitro. These data suggest an association between macrophage activation involved in rickettsial clearance and a transient immunosuppression.

Down‐Regulation of gp96 by Orientia tsutsugamushi

“…It was found that a transient immunosuppression in mice was demonstrable in O. tsutsugamushi infection (20). Silvered leaf monkeys inoculated with O. tsutsugamushi produced early leukocytosis followed by leukopenia and significant decrease in packed-cell volume (37).…”

The Th1/Th2-like switch in syphilitic infection: is it detrimental?

“…In chronic infections, organisms have evolved mechanisms to partially evade immune defenses. There are interesting parallels for chronic diseases caused by leishmaniae (10,14,32,42), trypanosomes (22,37,38,47), schistosomes (45,48,49,53), filariae (35), Mycobactenum leprae (46), Mycobactenum tuberculosis (40), Mycobactenum intracellulare (13), rickettsiae (21), and brucellae (12). An early acute stage of localized infection is typical.…”

“…PGE2 plays an important role in normal down-regulation of different immune responses. In certain infections, such as those caused by M. leprae (46), M. intracellulare (13), and Rickettsia tsutsugamushi (21), macrophages oversecrete PGE2. This accelerates the process of normal down-regulation.…”

“…By the time macrophages infiltrate on day 10, sufficient gamma interferon is present to quickly up-regulate these cells to a highly active state of phagocytosis. As treponemes are rapidly eradicated within 3 to 7 days, macrophages begin to produce excessive amounts of PGE2 as they do in chronic infections caused by R. tsutsugamushi (21), M. leprae (46), and M. intracellulare (13). This prostaglandin reaches critical levels too quickly and, as a result, directly inhibits T-helper cell synthesis of gamma interferon.…”

Candida mannan: chemistry, suppression of cell-mediated immunity, and possible mechanisms of action.

“…Establishing that prostaglandin production by monocytes is a component of immune dysfunction in CMC would have tremendous significance. This mechanism would (i) give the patient monocyte the role of suppressor cell (4), (ii) provide for the possibility that a suppressor T lymphocyte might also be involved (192), and (iii) allow classification of CMC with other chronic infections in which macrophages and T lymphocytes have a significant immunoregulatory role (19,24,41,70,71,87,103,113,126,130,177,181).…”