In Brief

Therapeutics

Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins Dadachova, E. et al. PLoS Med. 3, e427 (2006)

A proof of principle study recently published in PLos Medicine has demonstrated the effectiveness of radioimmunotherapy in targeting HIV-infected cells. Antibodies specific for the HIV-1 envelope glycoproteins gp120 and gp41 were labelled with either radioactive bismuth (²¹³Bi) or radioactive rhenium (¹⁸⁸Re). ACH-2 cells and HIV-infected peripheral blood mononuclear cells (PBMCs) were both selectively killed by radioisotope treatment in vitro. The treatment was also shown to be effective in vivo — in a SCID (severe combined immunodeficient) mouse model, >99% of the HIV-infected human PBMCs in the spleen were eliminated by gp41-specific antibodies labelled with²¹³Bi or ¹⁸⁸Re. The authors suggest that the major clinical use for HIV-targeting radioimmunotherapy could be as an adjunct to highly active antiretroviral therapy regimens.

Bacterial pathogenesis

Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells Worley, M. J. et al. Proc. Natl Acad. Sci USA 09 Nov 2006 (doi: 10.1073/pnas.0604054103)

Salmonella enterica serovar Typhimurium (S. typhimurium) is thought to be able to cross the intestinal barrier within CD18⁺ phagocytic cells. Phagocytes infected with S. typhimurium have been found to enter the bloodstream as quickly as 15 minutes after the organism has been ingested. What is responsible for the remarkable speed of this extraintestinal dissemination? Micah Worley and colleagues have been investigating this phenomenon, and specifically the role of SrfH, an S. typhimurium type III-secreted effector. CD18⁺ phagocytes were infected with wild-type S. typhimurium and an srfH mutant, and their ability to undergo chemotaxis was observed using a Boyden chamber. The results showed that SrfH stimulates phagocyte migration, and further work in a mouse model established that in vivo, SrfH accelerates the entry of S. typhimurium into the bloodstream.

Parasitology

Anopheles and Plasmodium : from laboratory models to natural systems in the field Cohuet, A. et al. EMBO Rep. 10 Nov 2006 (doi: 10.1038/sj.embor.7400831)

Interrupting the transmission of Plasmodium falciparum from human to human is a potential malaria-control strategy. The survival of the parasite to the oocyst stage within the vector is one of the stages that could potentially be targeted in malaria control, as shown by previous gene-silencing studies using the rodent malaria parasite Plasmodium berghei, which highlighted a strong positive or negative role for three Anopheles gambiae genes, CTL4, CTLMA2 and LRIM1. Now, Cohuet et al. report the results of the first gene-silencing studies using sympatric natural P. falciparum isolates and A. gambiae mosquitoes to look at the effects of these genes under near-natural conditions in Cameroon. The results showed that, in contrast with the results obtained previously using the P. berghei model, silencing of CTL4, CTLMA2 and LRIM1 had no effect on parasite development. This emphasizes the importance of studying the natural interactions between P. falciparum and A. gambiae as a follow up to laboratory work using model systems.