Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis.
BACKGROUND
Human African trypanosomiasis, caused by Trypanosoma brucei, involves an early hemolymphatic stage followed by a late encephalitic stage.


METHODS
We studied the expression of chemokines with use of microarray and enzyme-linked immunosorbent assay in T. brucei brucei-infected mice and in patients with human African trypanosomiasis and examined their role in controlling brain accumulation of T cells and parasites.


RESULTS
The messenger RNAs (mRNAs) encoding CXCR3 ligands CXCL9 and CXCL10 demonstrated the greatest increases among chemokines in brain specimens of infected mice, as determined by microarray. CXCL9 and CXCL10 mRNA accumulation was interferon (IFN)-gamma-dependent. Expression of CXCL10 was predominantly observed in astrocytes. Weight loss was registered in wild-type but not in CXCL10(-/-) and CXCR3(-/-) infected mice. Infected CXCL10(-/-) or CXCR3(-/-) mice demonstrated reduced accumulation of trypanosomes and T cells in the brain parenchyma but similar parasitemia levels, compared with wild-type mice. CXCL10 and IFN-gamma levels were increased in the cerebrospinal fluid of patients with late stage but not early stage human African trypanosomiasis. Levels of CXCL10 in patients with late stage human African trypanosomiasis were associated with somnolence, low body weight, and trypanosomes in the cerebrospinal fluid.


CONCLUSIONS
IFN-gamma-dependent CXCL10 is critical for accumulation of T cells and trypanosomes in the brain during experimental African trypanosomiasis. Data suggest CXCL10 as a candidate marker for late stage human African trypanosomiasis.
Amin
Daniel N
DN
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Rottenberg
Martin E
ME
Thomsen
Allan R
AR
Mumba
Dieudonné
D
Fenger
Christina
C
Kristensson
Krister
K
Büscher
Philippe
P
Finsen
Bente
B
Masocha
Willias
W
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000276:immunology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000276:immunology; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D014347:Trypanosoma brucei gambiense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015854:Up-Regulation
C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C515188:Cxcr3 protein, mouse; D012333:RNA, Messenger; D054367:Receptors, CXCR3