Khan Shariq A, Fidel Paul L, Thunayyan Awdah Al, Varlotta Sharon, Meiller Timothy F, Jabra-Rizk Mary Ann
Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, USA.
J AIDS Clin Res. 2013 Mar 5;4(193). doi: 10.4172/2155-6113.1000193.
HIV-infected individuals constitute a population highly susceptible to opportunistic infections, particularly oral candidiasis caused by the most pathogenic human fungal species . Host-produced salivary antimicrobial peptides are considered to be an important part of the host innate immune system involved in protection of the oral cavity against colonization and infection by microbial species. Histatin-5 (Hst-5) specifically has exhibited potent anti-candidal properties . However, its importance in protecting the oral mucosa against candidal colonization and importantly, its contribution to the observed enhanced susceptibility of HIV-infected individuals to candidiasis has not been previously investigated. To that end, a novel immunoassay was used to demonstrate significant decrease in salivary Hst-5 levels in HIV+ individuals concomitant with enhanced candidal prevalence. Further, saliva's anti-candidal potency was found to be proportional to Hst-5 concentration and significantly compromised in HIV+ subjects compared to controls. The key role for Hst-5 was further confirmed upon exposure to the Hst-5-specific antibody where saliva's initial killing activity was substantially compromised. Combined, these findings identify Hst-5 as a key anti-candidal salivary component and demonstrate its decreased levels in HIV infection providing new insights into oral Innate immune defense mechanisms and the enhanced susceptibility of HIV+ individuals to oral candidiasis.
感染艾滋病毒的个体是极易发生机会性感染的人群,尤其是由致病性最强的人类真菌物种引起的口腔念珠菌病。宿主产生的唾液抗菌肽被认为是宿主先天免疫系统的重要组成部分,参与保护口腔免受微生物物种的定植和感染。组蛋白5(Hst-5)尤其表现出强大的抗念珠菌特性。然而,其在保护口腔黏膜免受念珠菌定植方面的重要性,以及更重要的是,其对观察到的艾滋病毒感染者念珠菌病易感性增加的作用,此前尚未得到研究。为此,一种新型免疫测定法被用于证明,艾滋病毒阳性个体的唾液Hst-5水平显著下降,同时念珠菌患病率增加。此外,发现唾液的抗念珠菌效力与Hst-5浓度成正比,与对照组相比,艾滋病毒阳性受试者的唾液抗念珠菌效力显著受损。在暴露于Hst-5特异性抗体后,唾液的初始杀伤活性大幅受损,这进一步证实了Hst-5的关键作用。综合这些发现,确定Hst-5是唾液中关键的抗念珠菌成分,并证明其在艾滋病毒感染中的水平降低,为口腔先天免疫防御机制以及艾滋病毒阳性个体对口腔念珠菌病易感性增加提供了新的见解。