Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

Abstract

White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

Keywords: Geomyces destructans; Myotis lucifugus; cave-hibernating bats; hibernation-induced immune suppression; immune cell trafficking; immune reconstitution inflammatory syndrome (IRIS); white nose syndrome.

Figure 1. One of 30 little brown bats with white-nose syndrome collected from hibernation April 13, 2010 and taken into rehabilitation. Warmth, food and water were provided and this bat was photographed over time. Photographs were used with permission from Gregory Turner, Mick Valent and Jackie Kashmer. (A) Photograph taken with top lighting in hibernacula at collection April 13, 2010. No gross lesions can be seen, but the dusting of white material on the wing surface is evidence of fungal infection. (B) Photograph of bat (A) taken on April 29, 2010 after 16 d of rehabilitation. The transilluminated wing was photographed outstretched over a light box and shows a reticular pattern of wing damage. (C) Photograph of bat (A) taken May 11, 2010 shows progressively worsening of wing damage 29 d after being taken into rehabilitation. Loss of tissue is evident and the wing membrane is fragile. In the wild, without provision of food, water and protection, this bat would be unlikely to survive. (D) Photograph of bat (A) taken May 20, 2010, where there is evidence of wing healing 9 d after photograph 1C and 38 d of rehabilitation.

Figure 2. (A) Little brown bat found February 8, 2009 frozen outside of the small opening of a copper mine. The transilluminated wing was photographed outstretched over a light box and shows no evidence of wing damage. (B) Periodic acid Schiff stained section of wing membrane from bat (A) shows characteristic dense aggregates of robust hyphae forming a defined interface with the skin, erosion along the broad zone of skin contact (arrows) and no visible inflammatory response. (C) One of nine little brown bats that were found on the ground and unable to fly between April 4 and May 7, 2012. This bat was collected April 4, taken into rehabilitation, ate and drank, but died within 18 h of arrival. The wing was photographed outstretched over a light box and visible damage can be seen with dark areas of contraction and loss of elasticity. (D) Periodic acid Schiff stained section of wing membrane from the bat in (C). Severe neutrophilic inflammation and edema (bracket) in response to fungal hyphae (arrow). (E) Different field from same slide as in (D) shows a thick layer of degenerating neutrophils (brackets) at the margins of a dense aggregate of fungal hyphae eroding epidermis (arrow). (F) Little Brown Bat in (C). Degenerating neutrophils (arrowheads) surround the dense aggregate of fungal hyphae (arrows).