CD16 Expression on Monocytes in Healthy Individuals but Not Schistosome-Infected Patients Is Positively Associated with Levels of Parasite-Specific IgG and IgG1

Human IgG1 antibody responses are associated with protection against Schistosoma haematobium infection and are now a target for schistosome vaccine development. This study aimed to investigate the relationship between total IgG and the IgG subclasses and the monocyte IgG receptor, known as FcγRIIIa or CD16, in schistosome exposed people. Systemic levels of schistosome-specific anti-adult worm total IgG and IgG subclass titres were measured by ELISA in 100 individuals from an S. haematobium endemic area in Zimbabwe and, using parametric statistical methods and regression analysis, related to the levels of CD16 expression on individuals' circulating monocytes, determined via flow cytometry. Monocyte CD16 expression rose with parasite-specific total IgG and IgG1 in healthy participants, but not in schistosome infected patients. Similar to parasite-specific IgG and IgG1, CD16 expression in healthy individuals is associated with protection against schistosome infection. This relationship indicates a mechanistic link between the innate and adaptive immune responses to helminth infection in protection against infection. Further understanding the elements of a protective immune response in schistosomiasis may aid in efforts to develop a protective vaccine against this disease.This work was supported by the World Health Organisation and the Wellcome Trust grant WT082028MA, the Thrasher Research Fund and the Medical Research Council grant LJA-544

Inflammation in autoimmunity: receptors for IgG revisited

During the past decade, our knowledge of Fc receptor interactions in inflammation has increased dramatically owing to the availability of single and multiple Fc-receptor-deficient mice. The deletion of activating Fc gamma receptors protects against inflammation in models of immune-complex-mediated diseases, whereas the deletion of inhibitory Fc gamma receptors triggers increased susceptibility to immune-complex-induced inflammation. These new insights have a profound impact on our understanding of inflammation in autoimmune diseases, such as systemic lupus erythematosus (SLE). Comprehending the complex interactions between activating and inhibitory Fc gamma receptors might lead to new therapeutic approaches for human diseases, including SLE

Evidence for an intracellular niche for Bordetella pertussis in broncho-alveolar lavage cells of mice

Bordetella pertussis can attach, invade and survive intracellularly in human macrophages in vitro. To study the significance of this bacterial feature in vivo, we analyzed the presence of viable bacteria in broncho-alveolar lavage (BAL) cells of mice infected with B, pertussis. We found B. pertussis to be present in a viable state in BAL fluid cells until at least 19 days after infection, suggesting B. pertussis to be able to survive in those cells. This intracellular niche may play an important role in the pathogenesis of pertussis. Pertussis toxin and the RGD sequence of the virulence factor filamentous hemagglutinin (FHA) both play a rule in the attachment of B. pertussis to human and mouse macrophages in vitro and Lye hypothesized these virulence factors to be required for invasion and subsequent intracellular survival of B. pertussis in macrophages in vivo. A B. pertussis double mutant, in which the FHA RGD motif was changed to RAD and the ptx genes were deleted, was also found in a viable state in BAL fluid cells, albeit at lower levels than the wild-type strain. In our model, uptake of B. pertussis by alveolar phagocytes in vivo is thus, at least in part, determined by the bacterial virulence factors FHA and pertussis toxin. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved