Modulation of Leukocytes by Exotoxins Produced by HAP Organisms

Abstract

The HAP group of organisms is comprised of small Gram-negative rods that can colonize the mucosal surface of the respiratory and genitourinary tracts. In some instances there is a clear relationship between a particular HAP species and its host of choice. In other cases the organism is more promiscuous and will colonize a number of host species. Depending on the HAP species involved, this colonization may be benign, resulting in little or no recognizable infection or host response in a healthy individual (Nicolet, 1990). Subsequent exposure to various types of stressors, or underlying infection with a virus or other pathogenic agent, can favor multiplication of HAP organisms that leads to clinical disease. Leukocytes provide a first line of cellular defense against invading microorganisms. As such, it is critically important for HAP organism to evade the antimicrobial activity of leukocytes if they are to multiply and cause clinical disease. HAP organisms have developed several strategies for doing this, including the production of antiphagocytic capsules and the release of exotoxins (leukotoxins) that inhibit leukocyte antimicrobial activity or kill the leukocytes (Czuprynski and Sample, 1990). More recently, it has become clear that smaller amounts of some of these leukotoxins can activate leukocytes to release oxygen radicals and other inflammatory mediators that likely contribute to the intense inflammation that characterizes many HAP infections (Czuprynski et al., 1991; Breider et al., 1991; Maheswaran et al., 1993; Udeze and Kadis, 1992). The purpose of this chapter is to provide a brief overview of these exotoxins, their relatedness among various HAP species, their differential effects on leukocyte populations, and the possible contributions of other bacterial components (i.e., lipopolysaccharide) to their biological effects.