Macrophage Activation and Functions during Helminth Infection: Recent Advances from the Laboratory Mouse

Table 1

Common and potential mouse strains and reagents to examine AAM functions during parasitic helminth infection.

Methodology	Effect	Limitation (major phenotype after helminth infection)	References
Deletion of phagocytes
Clodronate liposomes	Depletion of circulating phagocytes if intravenous administration	Difficult-to-control efficacy (reduced survival after S. haematobium infection, defect in H. polygyrus control)	[160]
Diphtheria toxin treatment
CD11b-DTR	Specific depletion of macrophages, monocytes, and granulocytes	Nonspecific	[145]
CCR2-DTR	Depletion of Ccr2^+ circulating monocytes	CCR2-independent monocyte functions cannot be investigated (severe acute weight loss in response to S. mansoni infection)	[88]
CX3CR1-DTR	Depletion of CX3CR1^+-patrolling monocytes	Not specific to patrolling monocytes	[161]
CD169-DTR	Specific depletion of CD169^+ cells	Target the majority of resident tissue macrophages in many tissues	[162]
Clec4F-DTR	Specific depletion of Küpffer cells	Induce major monocyte recruitment in the liver	[119]
Neutralizing or depleting antibodies
Anti-CCR2 Ab (clone MC-21)	Depletion of Ccr2^+ circulating monocytes	CCR2-independent monocyte functions cannot be investigated	[163]
Ym1 neutralizing antibodies	Ym1 blockade	Not restricted to macrophages (increased neutrophil infiltration and IL-17 production by γδ T cells)	[151]
Knockouts
Il4ra^−/−	Global defect in IL-4 and IL-13 signaling	Not restricted to macrophages (defect in nematode control and increased susceptibility to S. mansoni)	[54]; [86]
Arg1^−/−	Global defect in arginase 1	Not restricted to macrophages (increased immunopathology in BM chimeras to S. mansoni)	[144]
Mrc1^−/−	Global defect in CD206 (mannose receptor)	Not restricted to macrophages	[133]; [154]
Retnla^−/−	Global defect in Relm-α	Not restricted to macrophages (increased type 2 cell-mediated cytokine responses after helminth infection)	[58]
Chil1^−/−	Global defect in BRP-39	Not restricted to macrophages (increased IL-17 production by γδ T cells)	[151]
Chia1^−/−	Global defect in AMCase	Not restricted to macrophages (defect in the control of gastrointestinal nematodes)	[149]
Conditional knockdowns
Lyz2^creIl4ra^−/lox	Defect of IL-4 and IL-13 signaling in macrophages and neutrophils	Not specific to macrophages; IL-4Rα expression retained in immature Lyz2^low macrophages (no effect on nematode infection and conflicting results after S. mansoni infection)	[54]; [80]; [121]; [86]
Lyz2^creArg1^lox/lox	Knockdown of arginase 1 in macrophages and neutrophils	Not specific to macrophages; Arg1 expression retained in immature Lyz2^low macrophages? (increased type 2 immunity and collagen deposition in chronic schistosomiasis)	[40]
Tie2^creArg1^lox/lox	Knockdown of arginase 1 in hematopoietic and endothelial cells	Not specific to macrophages but Arg1—mainly restricted to macrophages and hepatocytes (increased type 2 immunity and collagen deposition in chronic schistosomiasis)	[40]