Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells

Jeffrey B. Lyczak; Gerald B. Pier

doi:10.1128/9781555818111.ch3

Chapter 3 : Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells

Authors: Jeffrey B. Lyczak¹, Gerald B. Pier¹

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Affiliations: 1: Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115

Content Type: Monograph

Publication Year: 2000

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818111

Chapter DOI: 10.1128/9781555818111.ch3

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Abstract:

Bacterial pathogens are faced with the seemingly difficult task of persisting within their host. Bacterial invasion into host epithelium was first reported in the mid-1980s, and the study of this phenomenon has progressed in recent years to provide a more mechanistic analysis of how invasion proceeds. An overview of bacterial uptake by nonprofessional antigen-presenting cells (APCs) must consider the relevant processes with regard to both the entry and survival of the bacterial pathogen and the response of the defending host. The adaptive immune response, while able to efficiently and specifically deal with an almost infinite number of foreign antigens, is severely handicapped by the 1- to 2-week lag period required to mount a response after first exposure to a foreign substance. Apoptosis may be necessary to trigger desquamation of bacterium-laden epithelial cells. Unable to desquamate because of their nonsurface location, subsurface corneal epithelial cells support the replication of internalized bacteria, which are protected from antibody, complement, and phagocytic cells. The biochemical basis of bacterial invasion into host epithelium has been a topic of intense investigation since the late 1980s. A fuller understanding of the relative importance of these mechanisms and of the interactions that occur between them will greatly assist future strategies for prophylactic or therapeutic intervention in bacterial infectious disease.

Citation: Lyczak J, Pier G. 2000. Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells, p 41-60. In Brogden K, Roth J, Stanton T, Bolin C, Minion F, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818111.ch3

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Consequences of Bacterial Invasion into Nonprofessional Phagocytic Cells

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FIGURE 1

Schematic diagram of the mucociliary clearance mechanism of the airway epithelium. The apical surface of the epithelial cells comprises many hairlike cilia, which beat in a synchronized fashion. This membrane surface is also covered with a biphasic mucous layer: the lower, or periciliary, layer is more fluid while the upper layer is more viscous. Bacteria get trapped in the viscous layer and are carried upward due to the ciliary beating and are eventually expectorated and swallowed.

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FIGURE 1

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FIGURE 2

A summary of epithelial cell receptors, which mediate adhesion and invasion of bacteria into epithelial cells. The bacterium shown is a generic diagram and contains elements of both gram-positive and gram-negative bacteria. LPS, lipopolysaccharide.

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FIGURE 2

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FIGURE 3

Mechanisms by which epithelial cells recruit and activate immune effector cells following epithelial cell infection. (A) Infected epithelial cells secrete proinflammatory cytokines such as IL-1β and TNF-α (which are chemotactic for a number of immune effector cells). (B) Infected epithelial cells begin to express class II MHC proteins on their surface, allowing them to function as “nonprofessional” APCs for helper T lymphocytes. (C) Infected epithelial cells undergo apoptosis. Apoptotic bodies released from dead cells are subsequently phagocytosed by dendritic cells, which then present antigens to T lymphocytes.

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FIGURE 3

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FIGURE 4

Expression of class II MHC by epithelial cells following internalization of bacteria. Step 1: synthesis of class II MHC can be induced by bacterial internalization through the apical plasma membrane or by exposure to a milieu of proinflammatory cytokines. Step 2: class II MHC is synthesized and intersects endocytic vacuoles containing endocytosed antigen. Step 3: vesicles containing complexes of bacterial antigens and nascent MHC protein are trafficked exclusively to the basolateral membrane of the epithelial cell, thus ensuring antigen presentation to T lymphocytes in the underlying submucosal tissue.

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FIGURE 4

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FIGURE 5

Diapedesis of neutrophils (shown in gray) disrupts tight junctions between epithelial cells (shown in white). The resulting disruption may provide an access point for bacteria (shown in black), allowing them to cross the epithelium and reach deeper tissues.

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FIGURE 5

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FIGURE 6

Invasion of bacteria into nonprofessional phagocytes allows bacterial proliferation and spread. Diagram A depicts the intracellular replication of bacteria within host epithelium, as has been demonstrated to occur in the case of several microorganisms including P. aeruginosa and serovar Typhi. Diagram B illustrates that invasion of bacteria into a nonprofessional phagocytic host can serve as a means of accessing deeper host tissues. The specific example shown in the figure depicts serovar Typhi passing through the intestinal epithelium to reach a host macrophage, which it then infects and uses to disseminate throughout the host's body.

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FIGURE 6

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FIGURE 7

Two models intended to explain the differential outcome of CFTRmediated internalization of P. aeruginosa in two different host tissues. (A) In the airway, internalization of P. aeruginosa induces apoptosis of bacterium-laden epithelial cells. These epithelial cells detach from the tissue and are expectorated, thus removing the bacteria they contain from the airways. It is possible that apoptotic bodies derived from the bacterium-laden cells are phagocytosed by dendritic cells and presented to helper T cells by the dendritic cell. (B) In the cornea, bacteria that breach the superficial, squamous epithelial cells are internalized by basal epithelial cells. Due to their anatomic location, the bacterium-laden epithelial cells are unable to desquamate and serve instead as a niche for the replication of intracellular bacteria.

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FIGURE 7

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FIGURE 8

Actin motility (also called “rocket motility”) of S. flexneri after its invasion of a host epithelial cell. (A) After invasion of the epithelial cell, Shigella escapes the endocytic vacuole and then forms actin filaments that propel the Shigella from its original host epithelial cell to adjacent cells. (B) Formation of actin filaments requires the participation of bacterial proteins such as IcsA, as well as the recruitment of host cytoskeletal elements vinculin and actin. Synthesis of IcsA is asymmetric on the bacterial cell, resulting in the formation of actin filaments on only one pole of the bacterium (the “old” pole). Vinculin binds IcsA, initiating the polymerization of actin.

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FIGURE 8

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