Expression of Genes Encoding Innate Host Defense Molecules in Normal Human Monocytes in Response toCandida albicans

Abstract

Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C. albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C. albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor ␤) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes.

Lack of Toll IL-1R8 Exacerbates Th17 Cell Responses in Fungal Infection

“…A number of studies has shown the important role of IL-1 and IL-1Rs in resistance to candidiasis (38,39,46). However, through different immune mechanisms, both IL-1␣ and IL-1␤, produced through transcription and translation by the host (47), are involved in host defense against the fungus and contribute to the production of IFN-␥ (39).…”

Insights into the pathobiology of Paracoccidioides brasiliensis from transcriptome analysis—advances and perspectives

“…Macrophages, neutrophils and peripheral blood mononuclear cells (PBMCs) respond to a broad range of microbial stimuli with common transcriptional activation programmes [32,36,50]. In this regard, microarray analyses have shown an increase of genes related to innate immunity in macrophages infected with Mycobacterium tuberculosis, C. albicans and A. fumigatus [35,36,51]. Recently, for the first time, Silva et al (in press) [52] used cDNA microarray analysis to identify differential genes of macrophages infected with P. brasiliensis that are related to several immune processes such as inflammation, cell membrane regulation, transcriptional regulation, signal transduction, and apoptosis.…”

“…In recent years, several approaches such as cDNA microarrays, cDNA representational difference analysis (RDA) and serial analysis of gene expression (SAGE) have been developed to identify general profiles of gene expression [32,33]. Specifically, the cDNA microarray technology has been applied to the analysis of bacterial and fungal interactions with phagocytes, thus identifying key effectors of pathogen virulence and host defence [32,[34][35][36].…”

“…brasiliensis has been shown to be refractory to classical genetic analysis. Recently, however, careful analyses have established that it has a genome of [26][27][28][29][30][31][32][33][34][35] Mb distributed in four or five chromosomes [3][4][5]. Ploidy is not consensual; some groups have proposed several isolates to be diploid [3,4], whereas other have used different techniques to propose that most isolates be either haploid or aneuploid [5].…”

Early expression of local cytokines during systemic Candida albicans infection in a murine intravenous challenge model

“…Candida albicans infection in a murine intravenous challenge model situation occurring in the affected organs undergoing C. albicans infection (8)(9)(10). Therefore, the aim of the present study was to assess the local cytokine production in various organs (spleen, kidney and brain) during systemic C. albicans infection, as local cytokine levels and activity are of considerably greater value for monitoring the pathological events in a target tissue, rather than systemic cytokine levels (11).…”