An immunohistochemical analysis of onchocercal nodules: evidence for an interaction between macrophage MRP8/MRP14 and adult Onchocerca volvulus

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Abstract
SUMMARY: 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. FcRl (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 (CDlIc, CD18) and MRP8/MRP14, and with MoAb 24. 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/MRPI4. 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. M RP8/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.