The Kallikrein-Kinin System: A Novel Mediator of IL-17-Driven Anti-Candida Immunity in the Kidney
Publication Date
November 04, 2016
Authors
Kritika Ramani, Abhishek V. Garg, Chetan V. Jawale, Heather R. Conti, et al
Volume
12
Issue
11
Pages
e1005952
DOI
https://dx.plos.org/10.1371/journal.ppat.1005952
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005952
Scopus
85002189001
Mendeley
http://www.mendeley.com/research/kallikreinkinin-system-novel-mediator-il17driven-anticandida-immunity-kidney
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Mendeley | Further Information

{"title"=>"The Kallikrein-Kinin System: A Novel Mediator of IL-17-Driven Anti-Candida Immunity in the Kidney", "type"=>"journal", "authors"=>[{"first_name"=>"Kritika", "last_name"=>"Ramani", "scopus_author_id"=>"56364368800"}, {"first_name"=>"Abhishek V.", "last_name"=>"Garg", "scopus_author_id"=>"55762568500"}, {"first_name"=>"Chetan V.", "last_name"=>"Jawale", "scopus_author_id"=>"36504183900"}, {"first_name"=>"Heather R.", "last_name"=>"Conti", "scopus_author_id"=>"24829419400"}, {"first_name"=>"Natasha", "last_name"=>"Whibley", "scopus_author_id"=>"55383801100"}, {"first_name"=>"Edwin K.", "last_name"=>"Jackson", "scopus_author_id"=>"7202526550"}, {"first_name"=>"Sruti S.", "last_name"=>"Shiva", "scopus_author_id"=>"7004561028"}, {"first_name"=>"William", "last_name"=>"Horne", "scopus_author_id"=>"56601177200"}, {"first_name"=>"Jay K.", "last_name"=>"Kolls", "scopus_author_id"=>"56761689700"}, {"first_name"=>"Sarah L.", "last_name"=>"Gaffen", "scopus_author_id"=>"6602496240"}, {"first_name"=>"Partha S.", "last_name"=>"Biswas", "scopus_author_id"=>"7202443643"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"pui"=>"613548286", "pmid"=>"27814401", "doi"=>"10.1371/journal.ppat.1005952", "issn"=>"15537374", "scopus"=>"2-s2.0-85002189001", "sgr"=>"85002189001"}, "id"=>"f54c92d7-bd6d-3d71-b7be-2dfcda12dc07", "abstract"=>"The incidence of life-threatening disseminated Candida albicans infections is increasing in hospitalized patients, with fatalities as high as 60%. Death from disseminated candidiasis in a significant percentage of cases is due to fungal invasion of the kidney, leading to renal failure. Treatment of candidiasis is hampered by drug toxicity, the emergence of antifungal drug resistance and lack of vaccines against fungal pathogens. IL-17 is a key mediator of defense against candidiasis. The underlying mechanisms of IL-17-mediated renal immunity have so far been assumed to occur solely through the regulation of antimicrobial mechanisms, particularly activation of neutrophils. Here, we identify an unexpected role for IL-17 in inducing the Kallikrein (Klk)-Kinin System (KKS) in C. albicans-infected kidney, and we show that the KKS provides significant renal protection in candidiasis. Microarray data indicated that Klk1 was upregulated in infected kidney in an IL-17-dependent manner. Overexpression of Klk1 or treatment with bradykinin rescued IL-17RA-/- mice from candidiasis. Therapeutic manipulation of IL-17-KKS pathways restored renal function and prolonged survival by preventing apoptosis of renal cells following C. albicans infection. Furthermore, combining a minimally effective dose of fluconazole with bradykinin markedly improved survival compared to either drug alone. These results indicate that IL-17 not only limits fungal growth in the kidney, but also prevents renal tissue damage and preserves kidney function during disseminated candidiasis through the KKS. Since drugs targeting the KKS are approved clinically, these findings offer potential avenues for the treatment of this fatal nosocomial infection.", "link"=>"http://www.mendeley.com/research/kallikreinkinin-system-novel-mediator-il17driven-anticandida-immunity-kidney", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>3, "Biochemistry, Genetics and Molecular Biology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>0}

Scopus | Further Information

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