Table 1.

Immunological actions of proteinases on the mammalian immune system that drive clinical manifestations of Leishmaniases

Proteinase classes		Leishmania species	Activities on mammalian host	References
Cysteine proteinase	CPA	L. (L.) infantum	Related to the ability to infect mammalian hosts cells in vitro;	[33]
	CPB	L. (L.) mexicana	Associated with a Th2 profile in BALB/c mice: inducing lesions; IL-4 and IL-5 production; inhibition of IL-12 production by cleaving NF-κB; inhibition of NO production by cleaving the STAT-1 and AP-1 transcription factors.	[34-42]
			Associated with a Th1 profile in C3HeB/FeJ and C57BL/6 mice: expression of Th1-associated cytokines;
		L. (L.) amazonensis	Associated with the cleavage of MHC class II gene products in mice;	[43-46]
			Epitopes from CPB COOH-terminal extension modulate infection in BALB/c and CBA mice: induce Th1 or Th2-related cytokines; stimulate CD8+ T lymphocytes;
			Endogenous CP inhibitors are related with immune modulation
		L. (L.) major	Associated with a Th1 profile and reduction of IFN-γ expression in C3HeB/FeJ mice;	[37]
		L. (L.) pifanoi	Reduces the percentage of infected murine macrophages when parasites are treated with an anti-C-terminal extension antibody	[47]
		L. (L.) chagasi	Associated with Th1 profile in asymptomatic patients and IFN-γ production in cell cultures;	[48]
			Related to Th1 and Th2 profiles in cells from symptomatic human patients and dogs: IFN-γ, IL-4 and IL-10 production in cell cultures;
	CPC	L. (L.) mexicana	Contributes to resisting killing by macrophages	[49-51]
		L. (L.) chagasi	Induces TGF-β expression in human cell culture	[52]
Metallo-proteinases	M8	Leishmania spp.	Related to the hydrolysis and inactivation of immunoglobulin G; Inactivation of C3b factor to complement C3bi; Adhesion and internalization in macrophages; downregulation of gp63 expression induces Th1 profile in mice; cleave NF-κB and prevent expression of IL-12 and iNOS in mice	[53-56]
		L. (L.) major	Associated with human NK cells proliferation and cleavage CD4 glycoprotein on human T cells in culture.	[57,58]
		L. (L.) mexicana	In murine bone marrow macrophages, interferes with signaling cascades and affects transcription factors by cleaving c-Jun, the central component of AP-1, alters signaling through cleavage-activated protein tyrosine phosphatases in murine macrophages	[59]
Serine proteinases	OPB	L. (L.) donovani	Allows parasites to infect the murine macrophage	[60,61]
		L. (L.) major	Related to maintenance of murine macrophage infection	[62]