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Cytokine profiles of filarial granulomas in jirds infected with Brugia pahangi.

ABSTRACT: BACKGROUND:A granulomatous inflammatory response develops in jirds infected subcutaneously or intraperitoneally with filarial nematodes namely Brugia pahangi and B. malayi. Previous studies by light and electron microscopy have shown cellular inflammatory responses in and around these granulomas. Furthermore, the cellular inflammatory responses of granulomas found in the lymphatics and peritoneal cavity appear to be similar. The purpose of this study was to determine the cytokine profiles of granulomas in the peritoneal cavity of B. pahangi-infected jirds and to determine whether the granulomas release any proinflammatory cytokines ex vivo. METHODS:A semiautomated quantitative polymerase chain reaction (Q-PCR) was performed on cDNA prepared from the granulomas of infected jirds to study the species-specific mRNA expression of IL-2, IL-4, IFN-gamma, IL-5, and IL-10. Genomic DNA was extracted from the granulomas, and parasite DNA was detected by Q-PCR by amplifying the HhaI repeat sequence. The levels of the inflammation-causing cytokines IL-6 and TNFalpha that were secreted by the granulomas were measured by cell-based assays. RESULTS:Florid granulomas showed higher levels of IFN-gamma than other cytokines, linking this Th1 cytokine to the granulomatous inflammation that develops in jirds and humans. IL-4 expression was much lower than that of IFN-gamma but higher than that of IL-10. A low level of IL-5 mRNA expression was detectable in all granulomas as was the level of IL-2 expression. The levels of the inflammatory cytokines IL-6 and TNFalpha, secreted by intact granulomas, spontaneously increased by 48 h after culture. Parasite antigen stimulation and subsequent release of IL-6 and TNFalpha by the granulomas indicated a moderate increase in the levels of these two cytokines. The amplification of the Brugia HhaI repeat DNA and Wolbachia 16S rDNA indicated worm components and bacterial components in the granulomatous tissue. CONCLUSION:Granuloma development in filarial infections is a complex process involving cellular reactions responding to parasite/bacteria and their components. The interactions between worm-derived granulomas and their hosts are dynamic and multifaceted. The data collected thus far suggest that the expression profiles of many of the measured cytokines in the lymphoid tissues of Brugia-infected jirds are different from those of the cytokines in granulomas. Moreover, granulomas have the ability to secrete the inflammatory cytokines IL-6 and TNFalpha.

SUBMITTER: Rao RU

PROVIDER: S-EPMC1479342 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Cytokine profiles of filarial granulomas in jirds infected with Brugia pahangi.

Rao Ramakrishna U RU Klei Thomas R TR

Filaria journal 20060316

<h4>Background</h4>A granulomatous inflammatory response develops in jirds infected subcutaneously or intraperitoneally with filarial nematodes namely Brugia pahangi and B. malayi. Previous studies by light and electron microscopy have shown cellular inflammatory responses in and around these granulomas. Furthermore, the cellular inflammatory responses of granulomas found in the lymphatics and peritoneal cavity appear to be similar. The purpose of this study was to determine the cytokine profile ...[more]

PMID: 16542426

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Project description:Brugia malayi and B. pahangi are two closely related nematodes that cause filariasis in humans and animals. However, B. pahangi microfilariae are able to develop in and be transmitted by the mosquito, Armigeres subalbatus, whereas most B. malayi are rapidly melanized and destroyed within the mosquito hemocoel. A cross-species microarray analysis employing the B. malayi V2 array was carried out to determine the transcriptional differences between B. malayi and B. pahangi microfilariae with similar age distribution.Following microarray data analysis, a list of preferentially expressed genes in both microfilariae species was generated with a false discovery rate estimate of 5% and a signal intensity ratio of 2 or higher in either species. A total of 308 probes were preferentially expressed in both species with 149 probes, representing 123 genes, in B. pahangi microfilariae and 159 probes, representing 107 genes, in B. malayi microfilariae. In B. pahangi, there were 76 (62%) up-regulated transcripts that coded for known proteins that mapped into the KEGG pathway compared to 61 (57%) transcripts in B. malayi microfilariae. The remaining 47 (38%) transcripts in B. pahangi and 46 (43%) transcripts in B. malayi microfilariae were comprised almost entirely of hypothetical genes of unknown function. Twenty-seven of the transcripts in B. pahangi microfilariae coded for proteins that associate with the secretory pathway compared to thirty-nine in B. malayi microfilariae. The data obtained from real-time PCR analysis of ten genes selected from the microarray list of preferentially expressed genes showed good concordance with the microarray data, indicating that the microarray data were reproducible.In this study, we identified gene transcripts that were preferentially expressed in the microfilariae of B. pahangi and B. malayi, some of which coded for known immunomodulatory proteins. These comparative transcriptome data will be of interest to researchers keen on understanding the inherent differences, at the molecular level, between B. malayi and B. pahangi microfilariae especially because these microfilariae are capable of surviving in the same vertebrate host but elicit different immune response outcomes in the mosquito, Ar. subalbatus.

Dataset Information

Cytokine profiles of filarial granulomas in jirds infected with Brugia pahangi.

Publications

Cytokine profiles of filarial granulomas in jirds infected with Brugia pahangi.

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