Myiasis after study trip to French Guiana.

Cutaneous myiasis is usually a harmless tropical disease caused by infestation with larvae from a variety of flies. Because of its rare occurrence in Europe, it is often misdiagnosed. Increased travel to tropical regions has correspondingly increased the number of cases observed in Europe. The furuncular type of cutaneous myiasis in a 31-year-old biology student was diagnosed upon his return from French Guiana. The student cultured one of the larvae to obtain a botfly. This case is discussed in the light of the current literature on pathogenesis, incidence and therapy of cutaneous myiasis.

TGF-beta-dependent suppressive function of Tregs requires wild-type levels of CD18 in a mouse model of psoriasis.

Dysfunctional Tregs have been identified in individuals with psoriasis. However, their role in the pathogenesis of the disease remains unclear. Here we explored the effect of diminished CD18 (beta2 integrin) expression on the function of CD4+CD25+CD127(-) Tregs using the Cd18 hypomorphic (Cd18hypo) PL/J mouse model of psoriasis that closely resembles the human disease. We found that reduced CD18 expression impaired cell-cell contact between Tregs and DCs. This led to dysfunctional Tregs, which both failed to suppress the pathogenic T cells and promoted the onset and severity of the disease. This failure was TGF-beta-dependent, as Tregs derived from Cd18hypo PL/J mice had diminished TGF-beta1 expression. Adoptive transfer of Tregs expressing wild-type levels of CD18 into affected Cd18hypo PL/J mice resulted in a substantial improvement of the psoriasiform skin disease, which did not occur upon coinjection of the cells with TGF-beta-specific neutralizing antibody. Our data indicate a primary dysfunction of Cd18hypo Tregs, allowing subsequent hyperproliferation of pathogenic T cells in the Cd18hypo PL/J mouse model of psoriasis. This study may provide a step forward in our understanding of the unique role of CD18 expression levels in avoiding autoimmunity.

The role of C5a in the innate immune response after experimental blunt chest trauma.

The inflammatory response after severe blunt chest trauma often leads to acute lung injury and acute respiratory distress syndrome which are associated with high mortality rates. Whereas the role of innate immunity in acute lung injury has been broadly investigated, the immune response after blunt chest trauma is still poorly understood. Therefore, the role of complement and neutrophils was determined in bilateral lung injury induced by a single blast wave. The following time-points were investigated posttrauma: sham, 1, 6, 12, and 24 h. There was a time-dependent systemic activation of complement as determined by CH-50 and presence of C5a-dependent chemotactic plasma activity. Moreover, factor H, a complement regulatory protein, was increased systemically and locally after injury. Anti-C5a treatment immediately after trauma ameliorated these peaks. After an initial systemic leukopenic phase, a marked leukocytosis occurred. The latter was normalized by C5a blockade. In parallel, white blood cell count in bronchioalveolar lavage fluids was increased as a function of time and was significantly decreased by anti-C5a treatment. Trauma-induced lung injury was also associated with dramatic changes in neutrophil function, namely early enhanced chemotaxis and phagocytosis, followed by prolonged functional defects-all of which were ameliorated by anti-C5a treatment. Furthermore, blockade of C5a ameliorated the buildup of the proinflammatory cytokine TNF-alpha, diminished the increase of cytokine-induced neutrophil chemoattractant 1, and altered the levels of the anti-inflammatory cytokine IL-10. These data suggest that blunt chest trauma leads to systemic activation of complement and robust C5a generation, which causes perturbations in defensive functions of neutrophils. Thus, C5a might represent a potential target for therapeutic immunomodulation to prevent immune dysfunctions post-trauma and thereby, perhaps, the progression to acute respiratory distress syndrome.

The role of complement, C5a and its receptors in sepsis and multiorgan dysfunction syndrome.

Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS.

Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans.

Sepsis is associated with extensive complement activation, compromising innate immune defenses, especially in neutrophils (PMN). Recently, a second C5a receptor (C5L2) was detected on PMN without evidence of intracellular signaling. The current study was designed to determine changes in C5L2 in blood PMN during sepsis. In vitro exposure of PMN to C5a, but not to fMLP, led to reduced content of C5L2. Following cecal ligation and puncture-induced sepsis in rats, PMN demonstrated a time-dependent decrease in C5L2. In vivo blockade of C5a during experimental sepsis resulted in preservation of C5L2. Similarly, PMN from patients with progressive sepsis showed significantly reduced C5L2 expression (n = 26), which was virtually abolished in patients who developed multiorgan failure (n = 10). In contrast, sepsis survivors exhibited retention of C5L2 (n = 12/13). The data suggest that C5L2 on PMN diminishes during sepsis due to systemic generation of C5a, which is associated with a poor prognosis.