RT Journal Article
SR Electronic
T1 Host-pathogen transcriptomics of macrophages, Mucorales and their endosymbionts: a polymicrobial pas de trois
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 580746
DO 10.1101/580746
A1 Poppy Sephton-Clark
A1 José F Muñoz
A1 Herbert Itabangi
A1 Kerstin Voelz
A1 Christina A Cuomo
A1 Elizabeth R Ballou
YR 2019
UL http://biorxiv.org/content/early/2019/03/20/580746.abstract
AB Mucorales spores, the causative agents of mucormycosis, interact with the innate immune system to cause acute, chronic, or resolving infection. Understanding the factors that influence disease initiation and progression is key to understanding mucormycosis and developing new treatments. Complicating this, mucormycosis can be caused by a number of species that span the Mucorales genus and may be host to bacterial endosymbionts. This study sets out to examine the differences between two species in the Mucorales order by characterising their differential interactions with the innate immune system, and their interactions with environmental bacterial endosymbionts. Through a holistic approach, this study examines the transcriptional responses of Rhizopus delemar and Rhizopus microsporus, two of the most commonly diagnosed species, to innate immune cells. This study also examines the immune cell response and assesses the variation in these responses, given the presence or absence of bacterial endosymbionts within the fungi. We see that the fungal response is driven by interaction with innate immune cells. The effect of the bacterial endosymbiont on the fungus is species specific, with a minimal in the absence of stress, but strongly influencing fungal transcripts during interaction with innate immune cells. In contrast, we observe that the macrophage response varies depending on the infecting fungal species, but also depending on endosymbiont status. The most successful macrophages elicit a pro-inflammatory response, and we see that through germination inhibition macrophage survival is enhanced. This work reveals species-specific host responses to related Mucorales spores and shows that bacterial endosymbionts impact the innate immune cell response.