Host resistance to primary and secondary Campylobacter jejuni infections in C57Bl/6 mice

Abstract

Campylobacter jejuni has been known as a main causative agent of human enterocolitis for more than 30 years. This has prompted the research on defence mechanisms of the host involved. Although the humoral immune response to C. jejuni has been addressed in many studies, relatively little is known about the role of T lymphocytes in campylobacteriosis.

The current study was based on in vivo T-cell subsets depletion to evaluate the role of CD4⁺ and CD8⁺ T lymphocytes in disseminated C. jejuni infection in C57BL/6 mice. Depletion of either CD8⁺ or CD4⁺ cells did not change the overall infection kinetics of primary campylobacteriosis. To assess the role of T cells in acquired immunity that develops during primary infection in C57BL/6 mice, in vivo depletions were performed during reinfection. Depletion of CD4⁺ cells did not have any effect on secondary infection kinetics, whereas depletion of CD8⁺ cells resulted in secondary liver infection that failed to resolve during the observed period.

This study showed that both CD8⁺ and CD4⁺ T cells contribute to protection of C57BL/6 mice against C. jejuni. However, the predominant role resides in the CD8⁺ cell subpopulation. The exact mechanisms by which CD8⁺ cells operate during the course of campylobacteriosis will be the subject of our further research.

Introduction

Campylobacter jejuni is a slime, curved, Gram negative, microaerophilic, motile rod. It has been known as a causative agent of human enterocolitis since the 1970s when selective isolation media were developed [1]. The bacterium colonizes the small and large intestines, causing inflammatory diarrhea with fever. Currently, all over the world, C. jejuni is isolated more often than both the gastroenteric pathogens Salmonella and Shigella together [2], [3]. Campylobacter enteritis is usually a self-limited disease, but bacteremia and extraintestinal manifestations like meningitis, cholecystitis, urinary tract infections or septic abortions may occure. Additionally, C. jejuni has been estimated to be the trigger to almost half of all cases of Guillain–Barré syndrome, the less common but potentially more devastating postinfectious sequelae [4], [5].

Although nonspecific defenses such as gastric acidity and intestinal transit time are important in the pathogenesis of campylobacteriosis, these mechanisms are not sufficient to prevent colonization and subsequent inflammation. It is known that in patients with campylobacter enteritis, strong local and serum antibody response develops. The essential role of humoral immunity against C. jejuni has been confirmed in patients with congenital or acquired hypogammaglobulinemia, who are at increased risk for severe recurrent bacteremic infections [6], [7]. In addition to humoral immune deficiency, preexisting cellular immune disorders may increase the rate of Campylobacter enteritis. Higher incidence of C. jejuni infections among persons with AIDS has pointed to the possible involvement of cellular immune mechanisms [8]. However, the role of cell-mediated immunity to this pathogen has only been explored in recent years and is still poorly understood. It has been documented that C. jejuni is able to invade different host cells. It can persist and multiply within intestinal epithelial cells and macrophages in vitro. Immunohistological studies of gut tissue infected with C. jejuni suggest that intramacrophage survival occurs in vivo, as well. Prolonged intra-phagocytic survival may be one of the leading reasons for the development of bacteremia during C. jejuni infection [9].

We have previously established an experimental model of murine campylobacteriosis. It proved to be a useful in vivo model to demonstrate bacterial dissemination and tissue invasion. Intraperitoneal injection of mice was followed by systemic C. jejuni spread and colonization of internal organs [10]. The plasma cytokine production, esspecially interferon-gamma, was induced. However, the lack of interleukin-6 during the entire course of primary infection, supports the opinion that C. jejuni is not a typical extracellular bacterium [11].

The current study was based on in vivo subset depletion to evaluate the role of CD4⁺ and CD8⁺ T lymphocytes in disseminated C. jejuni infection. Depletion of either CD8⁺ or CD4⁺ cells did not change the overall infection kinetics of primary campylobacteriosis. To assess the role of T cell subsets in acquired immunity that develops during primary infection in C57BL/6 mice, in vivo depletions were performed during reinfection. Depletion of CD4⁺ cells did not have any effect on secondary infection kinetics, whereas depletion of CD8⁺ cells resulted in secondary liver infection that failed to resolve during the observed period.