scholarly journals The Jak/Stat pathway mediates disease tolerance during systemic bacterial infection in Drosophila

2021 ◽  
Author(s):  
Arun Prakash ◽  
Mickael Bonnet ◽  
Katy M. Monteith ◽  
Pedro F. Vale

Disease tolerance describes a hosts ability to maintain health independently of the ability to clear microbe loads. However, we currently know little about the mechanisms that underlie disease tolerance or how known mechanisms of tissue damage signalling and repair may contribute to variation in tolerance. The Jak/Stat pathway plays a pivotal role in Drosophila humoral innate immunity, signalling tissue damage and triggering cellular renewal, making it a potential mechanism underlying the disease tolerance phenotype. Here, we show that disrupting the Jak/Stat pathway in Drosophila melanogaster alters disease tolerance during Pseudomonas entomophila systemic infection. Overall, flies with disrupted Jak/Stat show variation in survival that is not explained by variation in pathogen loads. For instance, mutations disrupting the function of ROS producing dual oxidase (duox) or the negative regulator of Jak/Stat, Socs36E render males less tolerant to systemic bacterial infection but not females. We also investigated whether the negative regulator of Jak/Stat, G9a which has previously been associated with tolerance of viral infections is also implicated in tolerance of bacterial infection. While female flies lacking G9a showed higher mortality and reduced bacterial clearance, disease tolerance did not differ between G9a mutants and the wildtype. This suggests that G9a does not affect tolerance during systemic bacterial infection as it appears to do with viral infection. Overall, our findings highlight that Jak/Stat signalling mediates disease tolerance during systemic bacterial infection and that this response differs between males and females. Our work therefore suggests that differences in Jak/Stat mediated disease tolerance may be a potential source of sexually dimorphic response to infection in Drosophila.

2016 ◽  
Author(s):  
Radhakrishnan B. Vasanthakrishnan ◽  
Gupta Vanika ◽  
Jonathon Siva-Jothy ◽  
Katy M. Monteith ◽  
Sam P. Brown ◽  
...  

AbstractWolbachia-mediatedprotection against viral infection has been extensively demonstrated in Drosophila and in mosquitoes that are artificially inoculatedwith D. melanogaster Wolbachia (wMel), but to date no evidence for Wolbachia-mediated antibacterial protection has been demonstrated in Drosophila.Here we show that D. melanogaster carrying wMel shows reduced mortality during enteric – but not systemic - infection with the opportunist pathogen Pseudomonas aeruginosa, and that protection is more pronounced in male flies. Wolbachia-mediated protection is associated with increased early expression of the antimicrobial peptide attacinA, followed by increased expression of a ROS detoxification gene (gstD8), and other tissue damage repair genes which together contribute to greater host resistance and disease tolerance. These results highlight that the route of infection is important for symbiont-mediated protection from infection, that Wolbachia can protect hosts by eliciting a combination of resistance and disease tolerance mechanisms, and that these effects are sexually dimorphic.


2021 ◽  
Author(s):  
Arun Prakash ◽  
Katy M. Monteith ◽  
Pedro F Vale

Many insects thrive on decomposing and decaying organic matter containing a large diversity of both commensal and pathogenic microorganisms. The insect gut is therefore frequently exposed to pathogenic threats and must be able not only to detect and clear these potential infections, but also be able to repair the resulting damage to gut tissues in order to tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance, and most of this knowledge stems from systemic infections. Here we investigated how well-described mechanisms that either prevent, signal, control, or repair tissue damage during infection contribute to the phenotype of disease tolerance during gut infection. We orally infected adult Drosophila melanogaster flies with the bacterial pathogen Pseudomonas entomophila in several loss-of-function mutants lacking epithelial responses including damage preventing dcy (drosocrystallin - a major component of the peritrophic matrix), damage signalling upd3 (unpaired protein, a cytokine-like molecule), damage controlling irc (immune-regulated catalase, a negative regulator of reactive oxygen species) and tissue damage repairing egfr1 (epidermal growth factor receptor). Overall, we detect effects of all these mechanisms on disease tolerance. The deterioration of the peritrophic matrix in dcy mutants resulted in the highest loss of tolerance, while loss of function of either irc or upd3 also reduced tolerance in both sexes. The absence of tissue damage repair signalling (egfr1) resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate P. entomophila infection, despite carrying greater microbe loads than males. Together, our findings provide empirical evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sex differences in these mechanisms could generate sexual dimorphism in immunity.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christina A. Rostad ◽  
Neena Kanwar ◽  
Jumi Yi ◽  
Claudia R. Morris ◽  
Jennifer Dien Bard ◽  
...  

Abstract Background Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. Methods We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. Results Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. Conclusions Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.


2002 ◽  
Vol 80 (9) ◽  
pp. 1578-1583 ◽  
Author(s):  
Christopher P Yourth ◽  
Mark R Forbes ◽  
Robert L Baker

A few studies have shown that male and female invertebrates differ in immunity and that these differences appear related to differences in sexual dimorphism and gender differences in life histories. Melanotic encapsulation of foreign objects in insects is one form of immunity. The damselfly Lestes forcipatus Rambur is moderately sexually dimorphic, and much is known about patterns of mass gain in congeners relating to differences in life history between males and females. In this study, females were more immunoresponsive than males under controlled temperatures, following emergence, and at a time when parasitic mites were challenging these hosts. However, males and females that overlapped in mass at emergence did not differ in their immune responses. Males in better condition at emergence were more immunoresponsive than lighter males, but this relation was not found in females. Sex differences in immune expression may have implications for how females versus males are able to deal with challenges from parasites, under varying environmental conditions.


2021 ◽  
Author(s):  
Thomas E White ◽  
Amy Locke ◽  
Tanya Latty

Abstract Structurally coloured sexual signals are a conspicuous and widespread class of ornament used in mate choice, though the extent to which they encode information on the quality of their bearers is not fully resolved. Theory predicts that signalling traits under strong sexual selection as honest indicators should evolve to be more developmentally integrated and exaggerated than nonsexual traits, thereby leading to heightened condition dependence. Here we test this prediction through examination of the sexually dimorphic faces and wings of the cursorial fly Lispe cana. Males and females possess structural UV-white and golden faces, respectively, and males present their faces and wings to females during close-range, ground-based courtship displays, thereby creating the opportunity for mutual inspection. Across a field-collected sample of individuals, we found that the appearance of the faces of both sexes scaled positively with individual condition, though along separate axes. Males in better condition expressed brighter faces as modelled according to conspecific flies, whereas condition scaled with facial saturation in females. We found no such relationships for their wing interference pattern nor abdomens, with the latter included as a nonsexual control. Our results suggest that the structurally coloured faces, but not the iridescent wings, of male and female Lispe cana are reliable guides to individual quality and support the broader potential for structural colours as honest signals. They also highlight the potential for mutual mate choice in this system, while arguing for one of several alternate signalling roles for wing interferences patterns among the myriad taxa which bear them.


2021 ◽  
Author(s):  
Miguel Landum ◽  
Marta Salvado Silva ◽  
Nelson Martins ◽  
Luís Teixeira

AbstractThe microbial community interacting with a host can modulate the outcome of pathogenic infections. For instance, Wolbachia, one of the most prevalent invertebrate endosymbionts, strongly increases resistance of Drosophila melanogaster and other insect hosts, to many RNA viruses. D. melanogaster is also in continuous association with gut bacteria, whose role in antiviral immunity is poorly characterized. Here we asked how gut-colonizing bacteria impact viral titres and host survival, and how these interact with route of infection or Wolbachia presence. We compared germ-free flies and flies associated with two gut bacteria species recently isolated from wild flies (Acetobacter thailandicus and Lactobacillus brevis). We found that Wolbachia-conferred protection to both DCV or FHV is not affected by the presence or absence of these gut bacteria. Flies carrying A. thailandicus have lower DCV loads than germ-free flies, upon systemic infection, but reduced survival, indicating that these bacteria increase resistance to virus and decrease disease tolerance. Association with L. brevis, alone or in combination with A. thailandicus, did not lead to changes in survival to systemic infection. In contrast to the effect on systemic infection, we did not observe an impact of these bacteria on survival or viral loads after oral infection. Overall, the impact of gut-associated bacteria in resistance and tolerance to viruses was mild, when compared with Wolbachia. These results indicate that the effect of gut-associated bacteria to different viral infections, and different routes of infection, is complex and understanding it requires a detailed characterization of several parameters of infection.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0237687
Author(s):  
Mariya P. Dobreva ◽  
Joshua G. Lynton-Jenkins ◽  
Jaime A. Chaves ◽  
Masayoshi Tokita ◽  
Camille Bonneaud ◽  
...  

Darwin’s finches are an iconic example of adaptive radiation and evolution under natural selection. Comparative genetic studies using embryos of Darwin’s finches have shed light on the possible evolutionary processes underlying the speciation of this clade. Molecular identification of the sex of embryonic samples is important for such studies, where this information often cannot be inferred otherwise. We tested a fast and simple chicken embryo protocol to extract DNA from Darwin’s finch embryos. In addition, we applied minor modifications to two of the previously reported PCR primer sets for CHD1, a gene used for sexing adult passerine birds. The sex of all 29 tested embryos of six species of Darwin’s finches was determined successfully by PCR, using both primer sets. Next to embryos, hatchlings and fledglings are also impossible to distinguish visually. This extends to juveniles of sexually dimorphic species which are yet to moult in adult-like plumage and beak colouration. Furthermore, four species of Darwin’s finches are monomorphic, males and females looking alike. Therefore, sex assessment in the field can be a source of error, especially with respect to juveniles and mature monomorphic birds outside of the mating season. We caught 567 juveniles and adults belonging to six species of Darwin’s finches and only 44% had unambiguous sex-specific morphology. We sexed 363 birds by PCR: individuals sexed based on marginal sex specific morphological traits; and birds which were impossible to classify in the field. PCR revealed that for birds with marginal sex specific traits, sexing in the field produced a 13% error rate. This demonstrates that PCR based sexing can improve field studies on Darwin’s finches, especially when individuals with unclear sex-related morphology are involved. The protocols used here provide an easy and reliable way to sex Darwin’s finches throughout ontogeny, from embryos to adults.


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