Understanding the role of antibodies in murine infections with Heligmosomoides (polygyrus) bakeri: 35 years ago, now and 35 years ahead

Abstract

SUMMARYThe rodent intestinal nematode H.p.bakeri has played an important role in the exploration of the host-parasite relationship of chronic nematode infections for over six decades, since the parasite was first isolated in the 1950s by Ehrenford. It soon became a popular laboratory model providing a tractable experimental system that is easy to maintain in the laboratory and far more cost-effective than other laboratory nematode-rodent model systems. Immunity to this parasite is complex, dependent on antibodies, but confounded by the parasite's potent immunosuppressive secretions that facilitate chronic survival in murine hosts. In this review, we remind readers of the state of knowledge in the 1970s, when the first volume of Parasite Immunology was published, focusing on the role of antibodies in protective immunity. We show how our understanding of the host-parasite relationship then developed over the following 35 years to date, we propose testable hypotheses for future researchers to tackle, and we speculate on how the new technologies will be applied to enable an increasingly refined understanding of the role of antibodies in host-protective immunity, and its evasion, to be achieved in the longer term.

Immunity to Helminths: Resistance, Regulation, and Susceptibility to Gastrointestinal Nematodes

“…Notably, more recent studies have confirmed and extended these observations using transgenic mice with deletions in various genes involved in antibody production, class switching, and interaction with cells or complement (48). The data revealed that antibody does not need to interact with cells via Fc receptors or complement to mediate protection (48,49). More recently, a role for antibody in controlling H. polygyrus bakeri during its brief intestinal phase has been described (50,51) and is discussed below.…”

The Essential Role Played by B Cells in Supporting Protective Immunity Against Trichuris muris Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background

“…More broadly, the role of B cells in immunity to gastrointestinal nematodes in general has been debated at length (41)(42)(43)(44). Proposed mechanisms include production of antibody (45) and, in keeping with the current study, promoting, and maintaining of primary and memory Th2 cells (46,47) via their ability to produce cytokines, especially IL-4 (41,48,49), and/or by expressing co-stimulatory molecules, including OX40L and CD40 (50,51).…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…Indeed in the context of Trichuris infections, evidence points toward antibody-independent worm expulsion mechanisms ( 169 , 170 ). However, for other rodent helminths, roles for antibody have been well-documented ( 171 , 172 ). For example, parasite-specific IgG1 is thought to play a role in immunity to the rodent hookworm Heligmosomoides polygyrus ( 173 ).…”