Innate and adaptive immunity in Candida albicans infections and saprophytism

Underlying acquired immunity to the fungus Candida albicans is usually present in adult immunocompetent individuals and is presumed to prevent mucosal colonization progressing to symptomatic infection. Exploration of immunological events leading to Candida resistance or susceptibility has indicated the central role of the innate and adaptive immune systems, the relative contribution of which may vary depending on the site of the primary infection. Nevertheless, acquired resistance to infection results from the development of Th1 responses. Cytokines produced by Thl cells activate phagocytic cells to a candidacidal state. In contrast, cytokines produced by Th2 cells inhibit Th1 development and deactivate phagocytic effector cells. Because reciprocal influences have been recognized between innate and adaptive Th immunity, it appears that an integrated immune response determines the life-long commensalism of the fungus at the mucosal level, as well as the transition from mucosal saprophyte to pathogen.     

The role of IL-13 in helminth-induced inflammation and protective immunity against nematode infections.

Helminth infections induce the production of type 2 cytokines, which contribute both to expulsion of the worms and inflammatory responses that can either protect or damage the host. Although IL-4 has been considered the most critical cytokine for both inflammation and protective immunity, recent observations indicate that IL-13 - a related cytokine - can have equal or even greater importance than IL-4 in inflammatory responses and host protection against infection.     

Innate immunity against moulds: lessons learned from invertebrate models

The emergence over the past two decades of invasive mycoses as a significant problem in immunocompromised patients underscores the importance of deciphering innate immunity against filamentous fungi. However, the complexity and cost of traditionally used mammalian model hosts presents a bottleneck that has limited the rate of advances in this field. In contrast, invertebrate model hosts have several important advantages, including simple immune systems, genetic tractability, and amenity to high-throughput experiments. The application of these models to studies of host-pathogen interactions is contingent on two tenets: (1) host innate defenses are preserved across widely disparate taxa, and (2) similar fungal virulence factors are operative in insects and in mammals. Validation of these principles paved the way for the use of invertebrates as facile models for studying invasive mould infections. These studies have helped shape our understanding of human pattern recognition receptors, phagocytic cell function and antimicrobial proteins, and their roles in host defense against filamentous fungi.     

Innate immunity in viral encephalitis: role of C5

The complement system is a critical component of both the innate and acquired immune systems. It is important in host defense against viruses, bacteria, and fungi for opsonization and for lysis of pathogens. However, activated complement can also cause tissue damage. There is compelling evidence that complement factors are presented in the central nervous system (CNS). Complement activation (by any of the three pathways: classical, alternate, and lectin) can lead to inflammation and tissue damage, while at the same time may also restrict certain pathogens in the CNS. C5a is formed by proteolytic cleavage C5. C5a is considered the most potent proinflammatory mediator, often called an anaphylotoxin. In this communication, we examine the roles of C5 (C5a) in vesicular stomatitis virus (VSV)-induced encephalitis. We found that C5a is produced during VSV infection, but C5-deficient mice had similar pathology as their controls. We concluded that C5 is not a critical factor in mediating the host response during VSV encephalitis.     

Innate immunity and graft rejection

Summary: Although innate immunity evolved to combat pathogens, increasing awareness of a pivotal role in driving and shaping adaptive immunity has prompted this review on the role of innate immunity in graft rejection. We present evidence that grafts, especially xenografts, elicit innate responses, required for adaptive immunity. Particular attention is paid to studies by ourselves and others demonstrating the important role of innate immunity in T‐cell trafficking. The mechanisms by which grafts elicit innate immunity are a fertile subject for further investigation and an important target for therapeutic intervention.     

Innate immunity against Granulibacter bethesdensis, an emerging gram-negative bacterial pathogen

Acetic acid bacteria were previously considered nonpathogenic in humans. However, over the past decade, five genera of Acetobacteraceae have been isolated from patients with inborn or iatrogenic immunodeficiencies. Here, we describe the first studies of the interactions of the human innate immune system with a member of this bacterial family, Granulibacter bethesdensis, an emerging pathogen in patients with chronic granulomatous disease (CGD). Efficient phagocytosis of G. bethesdensis by normal and CGD polymorphonuclear leukocytes (CGD PMN) required heat-labile serum components (e.g., C3), and binding of C3 and C9 to G. bethesdensis was detected by immunoblotting. However, this organism survived in human serum concentrations of ≥90%, indicating a high degree of serum resistance. Consistent with the clinical host tropism of G. bethesdensis, CGD PMN were unable to kill this organism, while normal PMN, in the presence of serum, reduced the number of CFU by about 50% after a 24-h coculture. This finding, together with the observations that G. bethesdensis was sensitive to H(2)O(2) but resistant to LL-37, a human cationic antimicrobial peptide, suggests an inherent resistance to O(2)-independent killing. Interestingly, 10 to 100 times greater numbers of G. bethesdensis were required to achieve the same level of reactive oxygen species (ROS) production induced by Escherichia coli in normal PMN. In addition to the relative inability of the organism to elicit production of PMN ROS, G. bethesdensis inhibited both constitutive and FAS-induced PMN apoptosis. These properties of reduced PMN activation and resistance to nonoxidative killing mechanisms likely play an important role in G. bethesdensis pathogenesis.