Research Article: Temporal induction of pro-inflammatory and regulatory cytokines in human peripheral blood mononuclear cells by Campylobacter jejuni and Campylobacter coli

Date Published: February 14, 2017

Publisher: Public Library of Science

Author(s): Eman Hamza, Sonja Kittl, Peter Kuhnert, Qijing Zhang.


Campylobacter jejuni along with C. coli are major cause of human gastroenteritis worldwide. So far, the human immune response against Campylobacter is not entirely clear. We hypothesize that it is coordinated by an interaction between pro-inflammatory and regulatory cytokines which is influenced by bacterial and host-individual differences. Accordingly, we used peripheral blood mononuclear cells (PBMC) from healthy donors to study the primary systemic immune response to C. jejuni and C. coli. PBMC were stimulated by different strains of C. jejuni and C. coli for three time points (5, 10, 24 hours). The production of the pro-inflammatory (IL-6, IL-8, IFN-γ) and the regulatory (IL-10) cytokines were measured by ELISA. All strains induced higher levels of IL-8 and IL-6 than IFN-γ and IL-10. In contrast to IL-8 and IL-6, IL-10 showed a steeper increase over time. While IFN-γ did not show any further increase between 10 and 24 hours. Interestingly, there was a significant correlation between IL-8 and IL-10 which peaked at 24 hours. Despite the variability of the used bacterial strains, their effect on cytokine production was less pronounced than the inter-person differences. The strongest significant effect of the strain was on the level of IL-10. IL-10 and IL-6 were significantly influenced by strain-person interaction. In conclusion, the systemic immune response to C. coli and C. jejuni is characterized by an early pro-inflammatory reaction with later initiation of regulatory immune response which is influenced mainly by the host, explaining the individual variations in disease severity. Additional work is needed to determine the cellular sources of the produced cytokines as well as the campylobacter molecules that might contribute to this stimulation.

Partial Text

Campylobacteriosis is the most common foodborne zoonosis in Europe with chicken constituting the main reservoir [1]. Most outbreaks in humans are related to chicken food or water-borne sources [2]. Humans can get infected with multiple Campylobacter species, while the most pathogenic are C. jejuni and C. coli causing gastroenteritis [3]. However, the illness is generally mild, some individuals develop severe post infectious sequelae such as irritable bowel syndrome, reactive arthritis and Guillain-Barré syndrome [4].

The human immune system consists of a network of multiple immune-regulatory control elements that coordinate the immune response elicited by infectious microbes [13]. So far, no studies have been undertaken to analyse whether the immune response against Campylobacter in humans is controlled by a balance between pro-inflammatory and regulatory cytokines. Therefore, the aim of the present study was to examine the primary systemic immune response of the two medically important Campylobacter species C. jeuni and C. coli on PBMC from healthy individuals. Our results show significant effect of persons on both pro-inflammatory (IL-8, IL-6, IFN-γ) and regulatory (IL-10) cytokines in response to stimulation with Campylobacter. This might be linked to individual variations in the constitutive expression levels of toll-like receptors (TLR) [23] which recognize pathogen associated molecular patterns (PAMPs) and generate signals that promote an immune response [13]. Consistent with this explanation, we found that the production of pro-inflammatory (IL-8, IL-6, IFN-γ) cytokines by LPS is significantly influenced by persons (S1 Table).




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