# Strategies and limitations of the bat immune response to Pseudogymnoascus destructans: the causative agent of white-nose syndrome

## TL;DR

White-nose syndrome is devastating bat populations in North America, and this paper explores how bat immune responses, particularly Th17 and Th1 pathways, influence their ability to fight the fungal infection.

## Contribution

The paper identifies Th17 over-skewing as a potential maladaptive immune response in North American bats infected with Pseudogymnoascus destructans.

## Key findings

- North American bats show limited early mobilization of innate immune cells like macrophages and neutrophils against P. destructans.
- A Th17-type immune response is associated with poor outcomes, while a Th1 response is more effective in controlling the fungal infection.
- Antibody-mediated immunity helps reduce wing lesions but is not the main mechanism for fungal clearance.

## Abstract

The rapid spread of white-nose syndrome (WNS), an invasive fungal pathogen in bats caused by the psychrophilic fungus Pseudogymnoascus destructans, represents one of the most severe ongoing wildlife disease crises in North America. Since its emergence in 2006, WNS has driven drastic population declines in several ecologically and economically important bat species, including Myotis lucifugus. Once widespread and abundant, M. lucifugus is now designated as vulnerable or endangered in several jurisdictions, such as under Ontario’s Species at Risk Act (SARA). Despite this, current gaps in understanding the host-pathogen interactions underlying WNS have created uncertainty about which physiological or immunological pathways should be targeted for potential mitigation strategies. The infection produces lesions on the wing and tail membranes of the host, leading to excessive arousals from hibernation and premature depletion of overwinter fat reserves. Early defense begins on the skin, with inhibitory microbiota and acidic conditions assisting in the prevention of fungal germination. Upon infection, fungal antigens are recognized by pattern recognition receptors including toll-like receptors (TLRs) and C-type lectin receptors (CLRs), which trigger a cascade of cytokines that elicit the acute phase response (APR). This process typically initiates recruitment of innate immune cells for fungal clearance, such as macrophages and neutrophils, although North American bats show limited success in early mobilization of these cells to sites of infection. This failure to respond effectively is likely a result of an over-skewing towards a T-helper (Th)17-type response, identified by upregulation of cytokines such as interleukin (IL)-6, transforming growth factor (TGF)β, and IL-23. In contrast, P. destructans incites a Th1-skewed response in vaccine-challenged bats, which proves to be more effective in controlling fungal proliferation and suggests antagonism between the two response phenotypes. Antibody-mediated immunity appears to assist in survival, but is not a primary mechanism for fungal clearance, instead contributing to the prevention of excessive wing lesions. Discerning the immunological differences between susceptible and resistant bat populations is essential for developing effective strategies to mitigate the impact of WNS and may reveal novel insights into the complexity and potentially maladaptive nature of Th17 responses in North American bats.