Lunes 18 de Febrero de 2008; 10:00 hrs.

Methamphetamine Inhibits Antigen Processing, Presentation, and Phagocytosis

 

• Tallóczy Z, Martinez J, Joset D, Ray Y, Gácser A, et al. PLoS Pathogens Vol. 4, No. 2, e28 doi:10.1371/journal.ppat.0040028
• Methamphetamine (Meth) is abused by over 35 million people worldwide. Chronic Meth abuse may be particularly devastating in individuals who engage in unprotected sex with multiple partners because it is associated with a 2-fold higher risk for obtaining HIV and associated secondary infections. We report the first specific evidence that Meth at pharmacological concentrations exerts a direct immunosuppressive effect on dendritic cells and macrophages. As a weak base, Meth collapses the pH gradient across acidic organelles, including lysosomes and associated autophagic organelles. This in turn inhibits receptor-mediated phagocytosis of antibody-coated particles, MHC class II antigen processing by the endosomal–lysosomal pathway, and antigen presentation to splenic T cells by dendritic cells. More importantly Meth facilitates intracellular replication and inhibits intracellular killing of Candida albicans and Cryptococcus neoformans, two major AIDS-related pathogens. Meth exerts previously unreported direct immunosuppressive effects that contribute to increased risk of infection and exacerbate AIDS pathology....Más.

 

Martes 12 de Febrero de 2008; 10:16 hrs.

A calculated response: control of inflammation by the innate immune system

• Gregory M. Barton. J. Clin. Invest. 118(2): 413-420 (2008). doi:10.1172/JCI34431.
• Inflammation is a rapid yet coordinated response that can lead to the destruction of microbes and host tissue. Triggers capable of inducing an inflammatory response include tissue damage and infection by pathogenic and nonpathogenic microbes. Each of these triggers represents a qualitatively distinct stress to the host immune system, yet our understanding of whether they are interpreted as such remains poor. Accumulating evidence suggests that recognition of these distinct stimuli converges on many of the same receptors of the innate immune system. Here I provide an overview of these innate receptors and suggest that the innate immune system can interpret the context of an inflammatory trigger and direct inflammation accordingly......Más.

 

Viernes 25 de Enero 2008; 11:33 hrs.

Inflammation and Prostate Cancer: A Future Target for Prevention and Therapy?

• David Stock , Patti A. Groome , D. Robert Siemens. Urologic Clinics of North America- 2008 February (Vol. 35, Issue 1, Pages 117-130, DOI: 10.1016/j.ucl.2007.09.006). Given its long natural history, prostate cancer has become an ideal model for the clinical and basic science study of neoplastic disease in distinct pathologic phases: tumor initiation, progression, invasion, and metastasis. Chronic or recurrent acute inflammation, a product of infectious agents or other sources, has potential promotional roles in each of these phases. Nonsteroidal anti-inflammatory drugs (NSAIDs), because of their ability to attenuate inflammation, as well as possibly direct anti-cancer properties associated with the inhibition of stromal cyclooxygenase-2, are potential candidates for clinical use in prostate cancer. Though epidemiologic evidence indicating a reduced risk of prostate cancer for NSAID users supports a chemoprotective benefit, observational assessment and clinical trials of these agents among large cohorts of prostate cancer patients are needed to determine their value in prostate cancer management......Más.