Role of chemokines and cytokines in the neuropathogenesis of African trypanosomiasis

Table 1 Cytokines and chemokines with increased expression in the brain parenchyma of rodents and cerebrospinal fluid of human patients, more during late than early stage African trypanosomiasis

Site	Cytokine/chemokine	Ref.
Chemokines
Rodent brain parenchyma	CCL21, CCL4, CCL5, CCL7, CCL9, CCL12, CCL19, CCL28 CXCL1, CXCL5, CXCL9, CXCL101, CXCL12, CXCL131, CXCL14, CXCL16	[5,19]
HAT patient CSF	CCL21, CCL3, CXCL8 (IL-8), CXCL101, CXCL131	[5,7,8,20-25]
Cytokines
Rodent brain parenchyma	IFN-γ1, IL-1α, IL-1β1, IL-6, IL-101, TGF-β, TNF-α1	[10,19,26-28,30]
HAT patient CSF	IFN-γ1, IL-1β1, IL-61, IL-101, TNF-α1	[5,7,8,20,22,32-34]

¹Expressed in both late stage rodent brains and HAT patients’ CSF. CCL: C-C motif chemokine; CSF: Cerebrospinal fluid; CXCL: C-X-C motif chemokine; HAT: Human African trypanosomiasis; IFN: Interferon; IL: Interleukin; TGF: Transforming growth factor; TNF: Tumor necrosis factor.

Table 2 Cytokines and chemokines involved in Trypanosoma brucei spp. neuroinvasion

Cytokine/Chemokine	Trypanosome levels in the brain parenchyma of transgenic mice compared to WT mice	Ref.
Chemokines
CXCL10	CXCl10-/- and CXCR3-/- mice had less trypanosomes in the brain parenchyma compared with WT mice.	[5]
Cytokines
IFN-α/β	IFN-α/βR-/- mice had slightly less trypanosomes in the brain parenchyma compared with WT mice.	[15]
IFN-γ	IFN-γ-/- and IFN-γR-/- had less trypanosomes in the brain parenchyma compared with WT mice. Trypanosomes accumulated in the perivascular compartment, confined between the endothelial and the parenchymal basement membranes, in certain areas of the brains of both transgenic mice	[10]
IL-12	IL-12P40-/- mice had less trypanosomes in the brain parenchyma compared with WT mice.	[10]
TNF-α	TNFR1−/− mice had less trypanosomes in the brain parenchyma compared with WT mice.	[15]

CXCL: C-X-C motif chemokine; IFN: Interferon; IL: Interleukin; TNF: Tumor necrosis factor; WT: Wild type.

Table 3 Selected cytokines and associated neurological and neuroendocrine features of African trypanosomiasis

Cytokine	Possible neurological and neuroendocrine features associated with	Ref.
IFN-γ	Sleep pattern disruptions, hyperalgesia/hyperesthesia and pain	[41,60]
IL1β	Hyperalgesia/ hyperesthesia and pain, neurodegeneration	[28,29,61]
IL-6	Hypopituitarism and endocrine dysfunctions, sleep pattern disruptions, hyperalgesia/ hyperesthesia and pain	[38]
TNF-α	Hypopituitarism and endocrine dysfunctions, sleep pattern disruptions, hyperalgesia/hyperesthesia and pain, neurodegeneration	[28,29,38,41]

IFN: Interferon; IL: Interleukin; TNF: Tumor necrosis factor.