Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Abstract

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity.

Eosinophils Mediate Protective Immunity against Secondary Nematode Infection

“…A recent report documented a requirement for eosinophils in protection against primary, but not secondary infection by Brugia malayi . Similar to our findings in primary or secondary infection by T. spiralis his protection is independent of either MBP or EPO (61). Other granule proteins, such as eosinophil cationic protein (ECP), appear to be potent toxins and may be important (50).…”

Eosinophils in Helminth Infection: Defenders and Dupes

“…In addition, granules released by eosinophils have profound effects on recruitment and activation of dendritic cells, which in turn promote the development of Th2 responses [71, 72]. More recently, eosinophils have been shown to contribute to suppression of goblet cell mucus production in the lung and the IgE response in infection by the filarial nematode, B. malayi, providing indirect evidence for eosinophil-derived mediators that support immune regulation [70]. Importantly, eosinophils are required for clearance of B. malayi microfilarae in primary infection [70].…”

Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin

“…Furthermore, eosinophil peroxidase (EPO) and major basic protein (MBP) are important in controlling infection to some parasites [118] but not others [116] showing a direct role for proteins produced by eosinophils following degranulation.…”