Alternatively activated macrophages in helminth infections

Abstract

Helminthic parasites can trigger highly polarized immune responses typically associated with increased numbers of CD4(+) Th2 cells, eosinophils, mast cells, and basophils. These cell populations are thought to coordinate an effective response ultimately leading to parasite expulsion, but they also play a role in the regulation of associated pathologic inflammation. Recent studies suggest that macrophages, conventionally associated with IFN-gamma-dominant Th1-type responses to many bacteria and viruses, also play an essential role in the Th2-type inflammatory response. These macrophages are referred to as alternatively activated macrophages (AAMPhis) as they express a characteristic pattern of cell surface and secreted molecules distinct from that of classically activated macrophages (CAMPhis) associated with microbe infections. In this review, we will discuss recent findings regarding the role of AAMPhis in the development of disease and host protection following helminth infection.

Figure 1. Macrophage differentiation in response to different pathogens

Depending on the cytokine environment, as well as the presence of specific pathogen associated structures, macrophages can differentiate into classically or alternatively activated macrophages. Helminths induce alternatively activated macrophages, which upregulate arginase and which may be important in several aspects of host protection: parasite resistance, dampening harmful associated inflammation, and wound healing necessary to repair the damage caused by these large invasive multicellular parasites. In contrast, many microbes trigger classically activated macrophages, which upregulate iNOS, resulting in nitric oxide production, and can contribute to pathologic inflammation.