|
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 | | | |
Lyz2creIl4ra−/lox | Defect of IL-4 and IL-13 signaling in macrophages and neutrophils | Not specific to macrophages IL-4Rα expression retained in immature Lyz2low macrophages (no effect on nematode infection and conflicting results after S. mansoni infection) | [54] [80] [121] [86] |
Lyz2creArg1lox/lox | Knockdown of arginase 1 in macrophages and neutrophils | Not specific to macrophages Arg1 expression retained in immature Lyz2low macrophages? (increased type 2 immunity and collagen deposition in chronic schistosomiasis) | [40] |
Tie2creArg1lox/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] |
|