An immunohistochemical analysis of onchocercal nodules: evidence for an interaction between macrophage MRP8/MRP14 and adult Onchocerca volvulus.
We have used a panel of MoAbs to investigate the phenotype of macrophages and other leucocytes infiltrating onchocercal nodules. Nodules were removed from individuals at the end of the second year of a community-based, placebo-controlled trial of annual ivermectin chemotherapy in northern Nigeria. No significant differences were seen in the distribution and phenotype of leucocytes in nodules from ivermectin- and placebo-treated individuals. Live adult worms were only seen in nine of the 21 nodules examined. Three regions were clearly discernible within nodules containing both live and dead worms; an outer fibrovascular capsule (zone A), an inner adult worm bundle with surrounding hyaline extracellular matrix interspersed with solitary cells (zone B), and a dense cellular infiltrate surrounding and in contact with a variable proportion of the worm (zone C). Macrophages were the predominant cell type in all zones of the nodule. Those in zone B were distinguished by their dendritic morphology and strong reactivity with MoAbs directed against class II molecules, FcRI (CD64) and CD68, whereas macrophages in zone C were larger, more heterogeneous in shape, and were distinguished by strong reactivity with MoAbs directed against CR4 (CD11c, CD18) and MRP8/MRP14, and with MoAb24. T cells were found primarily in zones A and C, whilst eosinophils were found in only six nodules. A unique staining pattern was seen using MoAbs reacting with the calcium-binding protein MRP8/MRP14. Most macrophages in zones A and B were negative; however, where the occasional positive macrophage was seen in zone B, MRP8/MRP14 was also found around the cell and on the neighbouring worm surface, giving the impression that MRP8/MRP14 was being secreted onto the adult worm. Macrophages in zone C were also MRP8/MRP14-positive, and often the whole infiltrate was surrounded with extracellular MRP8/MRP14, with greatest concentration seen adjacent to the worm. MRP8/MRP14 was not identified on the surface of microfilariae (MF) within the same nodules. Since MRP8/MRP14 was seen on the adult worm in the absence of a leucocytic infiltrate, it may have an early role to play in the immune response to Onchocerca volvulus.
Edgeworth
J D
JD
Department of Ophthalmology, Ahmadu Bello University, Kaduna, Nigeria.
Abiose
A
A
Jones
B R
BR
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D040501:Calgranulin A; D040502:Calgranulin B; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007559:Ivermectin / Q000627:therapeutic use; D007962:Leukocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D009549:Nigeria; D017181:Onchocerca volvulus / Q000276:immunology*; D009855:Onchocerciasis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D007559:Ivermectin