Helicobacter pylori and Host Response

Abstract

Helicobacter pylori, a pathogen infecting the gastric antrum of half of the adult population worldwide, is thought to be the major cause of acute and chronic gastroduodenal pathologies, including gastric and duodenal ulcer, gastric cancer and gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) (Marshall et al., 1994; Parsonnet et al., 1991; Wotherspoon et al., 1991). Despite a vigorous humoral response against H. pylori antigens, most of infected subjects fails to eliminate the pathogen spontaneously. As in other infectious diseases, besides the virulence of the pathogen, both the natural and the specific immune responses of the host are crucial for determining the outcome of the infection. The immune system has evolved different defence mechanisms against pathogens. The first defensive line is provided by 'natural' immunity, including phagocytes, T cell receptor (TCR) + T cells, natural killer (NK) cells, mast cells, neutrophils and eosinophils, as well as complement components and pro-inflammatory cytokines, such as interferons (IFNs), interleukin (IL)-1, IL-6, IL-12, IL-18 and tumor necrosis factor (TNF)-. The more specialized TCR + T lymphocytes provide the second defence wall. These cells account for the specific immunity, which results in specialized types of immune responses which allow vertebrates to recognize and clear (or at least control) infectious agents in different body compartments. Viruses growing within infected cells, are faced through the killing of their host cells by CD8+ cytotoxic T lymphocytes (CTL). Most of microbial components are endocytosed by antigen-presenting cells (APC), processed and presented preferentially to CD4+ T helper (Th) cells. Th cells co-operate with B cells for the production of antibodies which opsonize extracellular microbes and neutralize their exotoxins. This branch of the specific Th cell-mediated immune response is known as humoral immunity. Other microbes, however, survive within macrophages in spite of the unfavorable microenvironment and antigen-activated CD4+ Th cells are required to activate macrophages, whose reactive metabolites and TNF- finally lead to the destruction of the pathogens. This branch of the specific Th cell-mediated response is known as cell-mediated immunity (CMI). Most of successful immune responses involve both humoral and cell-mediated immunity. CD4+ Th cells can develop different polarized patterns of cytokine production, such as type1 or Th1, type-2 or Th2, type-17 or Th17 (Mosmann et al., 1986; Del Prete et al., 1991; Korn et al., 2009).