Contradictory Roles for Antibody and Complement in the Interaction of Brucella abortus with Its Host

Abstract

The ability of serum complement to kill bacteria has been linked to host resistance to Gram-negative bacteria. A mechanism for killing extracellular organisms during early invasion, following release from infected phagocytic cells, or during bacteremia would contribute to a host's ability to resist disease. In fact, the ability of serum complement to kill bacteria has been linked to disease resistance. Brucella abortus are Gram-negative intracellular pathogens. Resistance to these bacteria involves the coordinated activities of the cellular and humoral immune systems. The existence of serum-resistant forms of B. abortus has been established, and it has been shown that these bacteria can resist the killing action of complement even in the presence of specific antibody. Antibody is usually necessary for complement-mediated killing of smooth (virulent) forms of Gram-negative bacteria. An anomolous situation exists with some isolates of smooth B. abortus. Sera containing high titers of specific antibody do not support killing unless they are diluted. In the bovine, this phenomenon is associated with IgG1 and IgG2 antibodies. This finding may account for the lack of positive correlation between antibody levels and resistance to disease, which has led, perhaps wrongly, to the idea that antibody and complement are not important in resistance to brucellosis. Available evidence suggests that antibody may have contradictory roles in the interactions between a host and bacteria. Avirulent (rough) forms of the organism would be rapidly killed by complement shortly after invasion, but serum-resistant smooth forms of the organism would survive and invade resident phagocytic cells. During the process of invasion and phagocytosis, the bacteria would initiate an immune response. With time, some B. abortus organisms would be released from infected phagocytic cells. In the early stages of this process, the bacteria would encounter IgM antibody and low concentrations of IgG antibody. These would cause complement-mediated killing, and infection would be restricted to resident phagocytic cells. However, the immune response to B. abortus antigens would be intensified, and IgG antibody levels would increase. High concentrations of antibody do no support complement-mediated killing of extracellular B. abortus, but the bacteria would be opsonized by antibody and complement component fragments. This would lead to increased phagocytosis of extracellular B. abortus as they appear, and concomitant extension of disease. Because of high levels of antibody would block complement-mediated killing of B. abortus, resistance to disease at this point would be dependent on cell-mediated immunity.

Deletion ofwboAEnhances Activation of the Lectin Pathway of Complement inBrucella abortusandBrucella melitensis

“…abortus is due to effects of the classical and not the alternative pathway (9,13,22,23). In addition, our results provide evidence for the first time that MBL may also play a role in host defense against Brucella.…”

“…Strains VTRM1 and WRR51 are attenuated in mice (55; Nikolich, unpublished), but not as much as strains RB51 or RA1 (23,29,41,55). The reasons for the greater attenuation of RB51 are unknown but may be related to more profound deficiencies in OPS.…”

“…The A (abortus) antigen is a linear homopolymer of ␣1,2-linked-perosamine. The M (melitensis) antigen is a linear homopolymer of the same sugar in which four ␣1,2-linked-perosamine residues are ␣1,3-linked to the last monosaccharide of a pentasaccharide repeating unit (22,23). Although A and M antigens may be present alone or together on either B. abortus or B. melitensis, strain 2308 expresses almost exclusively A antigen and strain 16M expresses M antigen (30).…”

Multiple interleukin-18 injections promote both mouse Th1 and Th2 responses after sublethalEscherichia coliinfection

“…Binding IgM with bacteria and activation of the complement system by IgM can either induce the lysis of invading bacteria or enhance the opsonization of infectious particles for efficient phagocytosis by macrophages and neutrophils [20][21][22][23]. IgM is thus an important defence mechanism against bacteria which takes effect before the IgG-mediated defence mechanism begins.…”

Type 1 Fimbrial Adhesin FimH Elicits an Immune Response That Enhances Cell Adhesion of Escherichia coli

“…In the last decade, there has been a rising number of reports describing antibodies which actually enhance viral or bacterial infection and pathogenesis (5,7,16,28). One mechanism of this antibody-dependent enhancement (so-called ADE phenomenon) is based on the bound antibody interacting with the receptor on host cells directly or through intermediary molecules, like complement components (5,7,16). Another mechanism of ADE is based on antibody binding to microbial antigens that results in sequestering important targets from the immune defense mechanisms (28).…”