Impaired Endotoxin Detoxification as a Factor in Enhanced Endotoxin Sensitivity of Malaria Infected Mice

Loose, Leland D.; Trejo, Rafael A.; Luzio, N. R. Di

doi:10.3181/00379727-137-35669

Cited by 31 publications

(13 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this respect, LPS components have been used as malaria vaccine adjuvants to enhance the vaccine-directed immune response [28]. On the other hand the elevation of sCD14 in severe malaria could explain the impaired endotoxin detoxification as a factor in enhanced endotoxin sensitivity in malaria-infected mice [29]. sCD14 could promote (in concert with inflammatory cytokines) endothelial cell activation and thus adhesion molecule expression [30,31].…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

Wenisch

Parschalk

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Serum sCD14, tumour necrosis factor‐alpha (TNF‐α), IL‐6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram‐negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n=16) had higher levels than patients without renal failure (n=29) (8116+1440 μg/lversus 9453+1017 μg/lP<0.05) and both had higher levels than patients with septicaemia (6155+1635μg/l) and normal subjects (2776+747 μg/l). A significant correlation between sCD14 and IL‐6 (r=0.756) and TNF (r=0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

Wenisch

Parschalk

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…However, the reduction in T cell numbers is transient (49), and the restoration of their basal numbers does not restore their ability to specifically respond to malaria antigens (29), suggesting that other components of the immune system are also affected. Accordingly, various models of murine malaria have demonstrated that MØ functions (e.g., antigen presentation and microbicidal functions) (7, 10, 29, 50–54) are greatly altered during the course of infection, but the mechanisms involved in the functional modulation of MØ by Plasmodium are still incompletely understood. Several lines of evidence suggest that the parasite and its metabolites, principally hemozoin (HZ) and glycosylphosphatidylinositol (GPI), which are released into circulation during the intraerythrocytic cycle, could contribute to the activation and/or the suppression of the immune response (7, 52, 55, 56).…”

Section: Hz and Malariamentioning

confidence: 99%

Malarial Pigment Hemozoin and the Innate Inflammatory Response

et al. 2014

View full text Add to dashboard Cite

Malaria is a deadly infectious disease caused by the intraerythrocytic protozoan parasite Plasmodium. The four species of Plasmodium known to affect humans all produce an inorganic crystal called hemozoin (HZ) during the heme detoxification process. HZ is released from the food vacuole into circulation during erythrocyte lysis, while the released parasites further infect additional naive red blood cells. Once in circulation, HZ is rapidly taken up by circulating monocytes and tissue macrophages, inducing the production of pro-inflammatory mediators, such as interleukin-1β (IL-1β). Over the last few years, it has been reported that HZ, similar to uric acid crystals, asbestos, and silica, is able to trigger IL-1β production via the activation of the NOD-like receptor containing pyrin domain 3 (NLRP3) inflammasome complex. Additionally, recent findings have shown that host factors, such as fibrinogen, have the ability to adhere to free HZ and modify its capacity to activate host immune cells. Although much has been discovered regarding NLRP3 inflammasome induction, the mechanism through which this intracellular multimolecular complex is activated remains unclear. In the present review, the most recent discoveries regarding the capacity of HZ to trigger this innate immune complex as well as the impact of HZ on several other inflammatory signaling pathways will be discussed.

show abstract

“…bouis BCG, there was a rapid and significant increase in endotoxin sensitivity during the progress of infection (Benacerraf et al 1959, Clark 1978, Clark ef al. 1981, Trejo & di Luzio 1971, Suter et af. 1958.…”

Section: Discussionmentioning

confidence: 99%

Characterization of macrophage function in Mycobacterium lepraemurium‐infected mice: sensitivity of mice to endotoxin and release of mediators and lysosomal enzymes after endotoxin treatment

Gardner

Lawton

1983

Parasite Immunology

View full text Add to dashboard Cite

Mycobacterium lepraemurium (MLM) infection increases the sensitivity of mice to lipopolysaccharide (LPS) as do infections with other intracellular parasites. Tumour necrosis factor (TNF), lymphocyte activating factor (LAF) and increased levels of various lysosomal and cytoplasmic enzymes were found in serum samples taken 2 h after intravenous injection of a small dose of LPS suggesting that damage to a variety of cell types, including macrophages, had occurred. Sera from moribund MLM-infected mice not injected with LPS also demonstrated significant levels of TNF compared with controls. Intravenous injections of silica into leprous mice also led to increased levels of serum lysosomal and cytoplasmic enzymes but did not give rise to a significant amount of TNF or LAF. Moreover, in contrast to LPS treatment, the injection of silica did not lead to the death of leprous mice. These findings suggest that the phagocytic cells of the infected animals did not contribute to the production of these mediators after LPS challenge. Rather, the non-phagocytic granuloma macrophages or other unidentified cell types seemed to provide the main source of the monokines TNF and LAF in vivo in the present model. These mediators may have important implications for the immunopathology of MLM infection.

show abstract

Impaired Endotoxin Detoxification as a Factor in Enhanced Endotoxin Sensitivity of Malaria Infected Mice

Cited by 31 publications

References 12 publications

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

Malarial Pigment Hemozoin and the Innate Inflammatory Response

Characterization of macrophage function in Mycobacterium lepraemurium‐infected mice: sensitivity of mice to endotoxin and release of mediators and lysosomal enzymes after endotoxin treatment

Contact Info

Product

Resources

About