Candida albicans is able to proliferate in environments that vary dramatically in ambient pH, a trait required for colonising niches such as the stomach, vaginal mucosal and the GI tract. Here we show that growth in acidic environments involves cell wall remodelling which results in enhanced chitin and β-glucan exposure at the cell wall periphery. Unmasking of the underlying immuno-stimulatory β-glucan in acidic environments enhanced innate immune recognition of C. albicans by macrophages and neutrophils, and induced a stronger proinflammatory cytokine response, driven through the C-type lectin-like receptor, Dectin-1. This enhanced inflammatory response resulted in significant recruitment of neutrophils in an intraperitoneal model of infection, a hallmark of symptomatic vaginal colonisation. Enhanced chitin exposure resulted from reduced expression of the cell wall chitinase Cht2, via a Bcr1-Rim101 dependent signalling cascade, while increased β-glucan exposure was regulated via a non-canonical signalling pathway. We propose that this “unmasking” of the cell wall may induce non-protective hyper activation of the immune system during growth in acidic niches, and may attribute to symptomatic vaginal infection.
We estimated the seroprevalence of anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies in residents of African countries and explored its associated factors. We searched PubMed, EMBASE, PsycINFO, AMED, CINAHL, DOAJ and Google Scholar databases for peer reviewed articles and pre‐prints that reported anti‐SARS‐CoV‐2 antibody seroprevalence of general or specific human populations resident in Africa. The eligible studies were evaluated using Joana Briggs Institute prevalence critical appraisal tool. Twenty‐three studies involving 27,735 individuals were included in our paper. The pooled seroprevalence of anti‐SARS‐CoV‐2 antibodies in Africa was 22% (95%CI: 14–31) with very high heterogeneity ( I 2 = 100%, p < 0.001). Seroprevalence was highest in studies conducted in Central Africa compared to Southern Africa, West Africa, North Africa and East Africa respectively. The number of days between the first reported coronavirus disease 2019 case in each country and when a seroprevalence study was conducted was a significant moderator of seroprevalence. Seropositivity was numerically influenced by gender and age of the participants with males and those aged below 50 years being most affected with SARS‐CoV‐2 infection. The highest pooled seroprevalence in Africa reported in this review should be interpreted cautiously due to high heterogeneity between studies. Continued seroprevalence surveillance is warranted to establish Africa's transition towards herd immunity.
Candida albicans infections range from superficial to systemic and are one of the leading causes of fungus-associated nosocomial infections. The innate immune responses during these various infection types differ, suggesting that the host environment plays a key role in modulating the host–pathogen interaction. In addition, C. albicans is able to remodel its cell wall in response to environmental conditions to evade host clearance mechanisms and establish infection in niches, such as the oral and vaginal mucosa. Phagocytes play a key role in clearing C. albicans, which is primarily mediated by Pathogen Associated Molecular Pattern (PAMP)–Pattern Recognition Receptor (PRR) interactions. PRRs such as Dectin-1, DC-SIGN, and TLR2 and TLR4 interact with PAMPs such as β-glucans, N-mannan and O-mannan, respectively, to trigger the activation of innate immune cells. Innate immune cells exhibit distinct yet overlapping repertoires of PAMPs, resulting in the preferential recognition of particular Candida morphotypes by them. The role of phagocytes in the context of individual infection types also differs, with neutrophils playing a prominent role in kidney infections, and dendritic cells playing a prominent role in skin infections. In this review, we provide an overview of the key receptors involved in the detection of C. albicans and discuss the differential innate immune responses to C. albicans seen in different infection types such as vulvovaginal candidiasis (VVC) and oral candidiasis.
BackgroundReference ranges for haematological and other laboratory tests in most African countries are based on populations in Europe and America and, because of environmental and genetic factors, these may not accurately reflect the normal reference ranges in African populations. AimTo determine the distribution of haematological parameters in healthy individuals residing in Blantyre, Malawi. We also examined the effect of sociodemographic and nutritional factors on the haematological variables. MethodsWe conducted a proof-of-concept cross-sectional study, involving 105 healthy blood donors at Malawi Blood Transfusion Service in Blantyre. Eligible participants were HIV-negative males and females, aged 19 to 35 years, who did not have any evidence of acute or chronic illness, or bloodborne infection. We performed the haematological tests at the MalawiLiverpool Wellcome Trust laboratory in Blantyre, and the screening tests at Malawi Blood Transfusion Service laboratories. ResultsOut of 170 consenting healthy volunteers, haematological results were available for 105 participants. The proportions of results which were below the lower limit of the manufacturer's reference ranges were 35.2% (37/105) for haemoglobin, 15.2% (16/105) for neutrophils, 23.8% (25/105) for eosinophils, and 88.6 % (93/105) for basophils. The proportions of results that were above the upper limit of the manufacturer's reference ranges were 9.5% (10/105) for platelets and 12.4% (13/105) for monocytes. We also observed that the mean leucocyte and basophil counts were significantly higher in males than females (p = 0.042 and p = 0.015, respectively). There were no statistically significant differences in haematological results observed among different ethnic, age, and body mass index groups. Conclusions Over half of otherwise healthy study participants had at least one abnormal haematological result, using previously established foreign standards. More detailed studies are needed to establish locally relevant normal ranges for different age groups and other demographic characteristics of the Malawian population. This will lead to accurate interpretation of laboratory results.
Summary Candida albicans is a commensal of the urogenital tract and the predominant cause of vulvovaginal candidiasis (VVC). Factors that increase circulatory estrogen levels such as pregnancy, the use of oral contraceptives, and hormone replacement therapy predispose women to VVC, but the reasons for this are largely unknown. Here, we investigate how adaptation of C . albicans to estrogen impacts the fungal host-pathogen interaction. Estrogen promotes fungal virulence by enabling C . albicans to avoid the actions of the innate immune system. Estrogen-induced innate immune evasion is mediated via inhibition of opsonophagocytosis through enhanced acquisition of the human complement regulatory protein, Factor H, on the fungal cell surface. Estrogen-induced accumulation of Factor H is dependent on the fungal cell surface protein Gpd2. The discovery of this hormone-sensing pathway might pave the way in explaining gender biases associated with fungal infections and may provide an alternative approach to improving women's health.
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