E-Letter responses to:

reports: Nathan C. Peters, Jackson G. Egen, Nagila Secundino, Alain Debrabant, Nicola Kimblin, Shaden Kamhawi, Phillip Lawyer, Michael P. Fay, Ronald N. Germain, and David Sacks In Vivo Imaging Reveals an Essential Role for Neutrophils in Leishmaniasis Transmitted by Sand Flies Science 2008; 321: 970-974 [Abstract] [Full text] [PDF]

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Published E-Letter responses:

Response to B-Z Levi's E-Letter

David Sacks, Nathan Peters   (11 December 2008)

A Concern Toward Macrophage Data Detecting Leishmania in Mice

Ben-Zion Levi   (11 December 2008)

Response to B-Z Levi's E-Letter 11 December 2008
David Sacks, Head, Intracellular Parasite Biology Section Laboratory of Parasitic Diseases, NIAID, Bethesda, MD 20892, USA, Nathan Peters Respond to this E-Letter: Re: Response to B-Z Levi's E-Letter	The main findings (Reports, "In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies," by N. C. Peters et al., 15 August 2008, p. 970) point to a role for neutrophils in the initial uptake and subsequent survival and growth of Leishmania major at the site of their delivery by sand fly bite in the skin. The acute inflammatory, wound healing response involving neutrophils is highly conserved, and there is no evidence, so far as we are aware, to indicate that this response is different in B6/B10 Nramp1 mutant versus congenic Nramp1 wild type mice. Furthermore, the role of neutrophils in enhancing the subsequent uptake and survival of the parasite in macrophages (suggested by the neutrophil depletion experiments) would, if anything, be expected to be less pronounced in a mouse strain that is already compromised for intraphagosomal killing. David Sacks and Nathan Peters Laboratory of Parasitic Diseases, NIAID, Bethesda, MD 20892, USA.
A Concern Toward Macrophage Data Detecting Leishmania in Mice 11 December 2008
Ben-Zion Levi Department of Biotechnology and Food Engineering, Technion, Haifa 32000, Israel Respond to this E-Letter: Re: A Concern Toward Macrophage Data Detecting Leishmania in Mice	The Report by N. C. Peters et al. ("In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies," 15 August 2008, p. 970) is accompanied by a commentary in the same issue by B. John and C. A. Hunter (1). This study was performed in C57BL/6 mice and therefore raises a major concern that was not dealt with in the paper and the accompanying commentary. This mouse strain is very susceptible to intraphagosomal pathogens including Leishmania due to a point mutation in the Nramp1 gene also known as Slc11a1. Since Nramp1 is an important innate host resistance factor expressed exclusively in macrophage and dendritic cells, the concern is about the validity of the macrophage data. In addition, the fact that this mouse strain is already compromised for intraphagosomal pathogen killing ability raises the possibility that its initial response to Leishmania may be already compromised. It is possible that the observed response to the infection by Leishmania is already skewed towards granulocyte\neutrophils response rather than monocyte\macrophage, in analogy to a compensation of Th2 response when Th1 is compromised. Ben-Zion Levi Department of Biotechnology and Food Engineering, Technion, Haifa 32000, Israel. Reference 1. B. John, C. A. Hunter, Science, 321, 917 (2008).