GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi
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GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi. / Rauch, Jessica; Barton, Jessica; Kwiatkowski, Marcel; Wunderlich, Malte; Steffen, Pascal; Moderzynski, Kristin; Papp, Stefanie; Höhn, Katharina; Schwanke, Hella; Witt, Susanne; Richardt, Ulricke; Mehlhoop, Ute; Schlüter, Hartmut; Pianka, Verena; Fleischer, Bernhard; Tappe, Dennis; Osterloh, Anke.
in: PLOS ONE, Jahrgang 16, Nr. 6, e0253084, 2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - GroEL is an immunodominant surface-exposed antigen of Rickettsia typhi
AU - Rauch, Jessica
AU - Barton, Jessica
AU - Kwiatkowski, Marcel
AU - Wunderlich, Malte
AU - Steffen, Pascal
AU - Moderzynski, Kristin
AU - Papp, Stefanie
AU - Höhn, Katharina
AU - Schwanke, Hella
AU - Witt, Susanne
AU - Richardt, Ulricke
AU - Mehlhoop, Ute
AU - Schlüter, Hartmut
AU - Pianka, Verena
AU - Fleischer, Bernhard
AU - Tappe, Dennis
AU - Osterloh, Anke
PY - 2021
Y1 - 2021
N2 - Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.
AB - Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.
U2 - 10.1371/journal.pone.0253084
DO - 10.1371/journal.pone.0253084
M3 - SCORING: Journal article
C2 - 34111210
VL - 16
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
M1 - e0253084
ER -