A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice

Abstract

Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection.

First insights in the variability of Borrelia recurrentis genomes

“…The interest was raised both in clinicians and the research community. Cases of LBRF were reported in Germany [ 8 ], Italy [ 24 ], the Netherlands [ 25 ], Belgium [ 26 ], Finland [ 27 ] and Switzerland [ 28 , 29 ]. All cases were imported, and associated with newly arrived migrants, with a possible autochtonuous transmission in Italy [ 24 ].…”

“…The epidemiological investigations pointed to a common infection source along the Mediterranean migration route for refugees from East Africa [ 8 , 28 ]. The identical SNP pattern in refugee isolates supports this hypothesis, even in the light of the low variability of the B .…”

Borrelia persica Infection in Immunocompetent Mice - A New Tool to Study the Infection Kinetics In Vivo

“…microtti induced fever in white mice (mouse strain unknown; [ 14 ]). Nevertheless, our infection model could be useful for research, because it allows comparative studies with other RF spirochetes in mice [ 16 – 19 ].…”

“…persica in vitro [ 14 , 15 ]. However, for other RF borrelia species the mouse is usually considered to be the appropriate animal model [ 16 – 19 ] and Babudieri investigated relapsing fever in Jordan by injecting blood of diseased patients into mice in order to confirm TBRF spirochetosis [ 20 ]. The mice used in the experiment tested positive two to five days after injection.…”

Relapsing (recurrent) disease caused by Borrelia miyamotoi

“…существенные характеристики патогена могут меняться непосредственно в ходе заболевания. В опытах на животных последующие приступы боррелиозных возвратных лихорадок слабее, короче и характеризуются меньшим уровнем бактериемии [35,36]. Это можно объяснить накоплением антител к менее антигенным, но более консервативным белкам боррелий, например к белкам Fhbp, связывающим фактор H комплемента [37].…”