Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major.

Stenger, Steffen; Thüring, H; Röllinghoff, Martin; Bogdan, Christian

doi:10.1084/jem.180.3.783

Cited by 280 publications

(225 citation statements)

References 65 publications

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…We show that the lymph nodes and spleens of mice infected with any of the tested parasite strains are devoid of detectable iNOS mRNA during the first week. This is in agreement with experiments by Stenger et al in which infection of Balb/c with L. major did not result in substantial iNOS transcription until week 5 [28].…”

Section: Discussionsupporting

confidence: 93%

Experimental Infection of Balb/c Mice with Leishmania panamensis and Leishmania mexicana: Induction of Early IFN‐γ but not IL‐4 is Associated with the Development of Cutaneous Lesions

et al. 1997

View full text Add to dashboard Cite

Guevara-Mendoza O, Une C, Franceschi Carreira P, Ö rn A. Experimental Infection of Balb/c Mice with Leishmania panamensis and Leishmania mexicana: Induction of Early IFN-g but not IL-4 is Associated with the Development of Cutaneous Lesions. Scand J Immunol 1997;46:35-40 Resistance to the Leishmaniae is associated with interferon (IFN)-g mediated activation of macrophages. In this study, Balb/c mice were infected with three Leishmania strains that cause progressively growing cutaneous lesions without obvious dissemination; L. mexicana mexicana giving rise to rapidly growing lesions, and L. (Viannia) panamensis and L. mexicana-like, which both cause slowly developing lesions. The rate of lesion growth was compared to induction of early local and systemic IFN-g responses. All the three parasite strains induced increased levels of IFN-g transcripts 24 h after infection. Infection with the more aggressive strain resulted in a notably lower IFN-g response when compared to infection with the two low pathogenic strains. Interleukin-4 (IL-4) mRNA appeared 7 days after infection with L. (Viannia) panamensis and L. mexicana-like but not with L. mexicana mexicana. Thus, virulence of these Leishmania strains could not be associated with induction of IL-4 during the first week after infection. In addition, none of the Leishmania strains induced detectable mRNA for IL-12 or inducible nitric oxide synthase (iNOS). These data present a picture somewhat different from that which has been described in L. major experimental infection.

show abstract

Section: Discussionsupporting

confidence: 93%

Experimental Infection of Balb/c Mice with Leishmania panamensis and Leishmania mexicana: Induction of Early IFN‐γ but not IL‐4 is Associated with the Development of Cutaneous Lesions

et al. 1997

View full text Add to dashboard Cite

show abstract

“…2 shows that this is not the case. It can be seen, in agreement with some recent reports (17)(18)(19)(20)(21), that PEC from two Th1-like strains (C57BL/6 and B10D2) are more easily activated by IFN-␥ to produce NO than macrophages from the two Th2-like strains (BALB/c, DBA/2). The concentration of citrulline, the other product of the iNOS pathway, parallels that of NO, as would be expected.…”

Section: Differential Arginine Metabolism By Th1 and Th2 Macrophagessupporting

confidence: 81%

“…Whereas the aforementioned results clearly indicate that T lymphocytes from different strains of mice have a tendency to produce cytokines that activate or inhibit macrophages, other reports have shown that macrophages from the Th1 strains are more easily activated than those from Th2 strains (17)(18)(19)(20)(21). Thus, the ability to generate a Th1-or Th2-type response does not wholly depend on T lymphocytes.…”

mentioning

confidence: 75%

“…In addition, TGF-␤1 has been reported to increase arginase activity (47). In vivo, the level of TGF-␤ correlates with susceptibility to Leishmania (20,48,49). Also, inhibition of TGF-␤1 has been shown to heighten resistance to diseases, in which macrophages are the likely effector (50).…”

Section: Macrophage Tgf-␤1 Production Is Inversely Proportional To Mamentioning

confidence: 99%

See 1 more Smart Citation

M-1/M-2 Macrophages and the Th1/Th2 Paradigm

Mills

Kincaid

Alt

et al. 2000

The Journal of Immunology

2,643

2,164

View full text Add to dashboard Cite

Evidence is provided that macrophages can make M-1 or M-2 responses. The concept of M-1/M-2 fomented from observations that macrophages from prototypical Th1 strains (C57BL/6, B10D2) are more easily activated to produce NO with either IFN-γ or LPS than macrophages from Th2 strains (BALB/c, DBA/2). In marked contrast, LPS stimulates Th2, but not Th1, macrophages to increase arginine metabolism to ornithine. Thus, M-1/M-2 does not simply describe activated or unactivated macrophages, but cells expressing distinct metabolic programs. Because NO inhibits cell division, while ornithine can stimulate cell division (via polyamines), these results also indicate that M-1 and M-2 responses can influence inflammatory reactions in opposite ways. Macrophage TGF-β1, which inhibits inducible NO synthase and stimulates arginase, appears to play an important role in regulating the balance between M-1 and M-2. M-1/M-2 phenotypes are independent of T or B lymphocytes because C57BL/6 and BALB/c NUDE or SCID macrophages also exhibit M-1/M-2. Indeed, M-1/M-2 proclivities are magnified in NUDE and SCID mice. Finally, C57BL/6 SCID macrophages cause CB6F1 lymphocytes to increase IFN-γ production, while BALB/c SCID macrophages increase TGF-β production. Together, the results indicate that M-1- or M-2-dominant macrophage responses can influence whether Th1/Th2 or other types of inflammatory responses occur.

show abstract

“…A Th1 immune response leads to the induction of iNOS, which results in production of nitric oxide (NO), which is essential for killing the parasite. [14][15][16] In contrast, Th2 cytokines stimulate arginase production, which reduces killing capacity. [17][18][19] Therefore, proper activation and maturation of antigen-presenting cells (APCs) resulting in Th1 immunity is fundamental to parasite control.…”

Section: Discussionmentioning

confidence: 99%

Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice

Amaral¹,

Gomes-Santos²,

Paula-Silva³

et al. 2010

Immunology

View full text Add to dashboard Cite

Summary The immature immune system requires constant stimulation by foreign antigens during the early stages of life to develop properly and to create efficient immune responses against later infections. We have previously shown that intake of antigenic dietary protein is critical for inducing maturation of the immune system as well as for the development of T helper type 1 (Th1) immunity. In this study, we show that administration of an amino acid (aa)‐based diet during the development of the immune system subsequently resulted in inefficient control of Leishmania major infection in adult C57BL/6 mice. Compared with mice fed a control protein‐containing diet, adult aa‐fed mice showed a decreased interferon (IFN)‐γ response to parasite antigens and insufficient production of nitric oxide (NO), which is crucial to parasite death. However, no deviation towards Th2‐specific immunity to L. major was observed. Phenotypic analysis of antigen‐presenting cells (APCs) from aa‐fed mice revealed deficient levels of the costimulatory molecules CD40 and CD80, and low levels of interleukin (IL)‐12 produced by peritoneal macrophages, revealing an early stage of maturation of these cells. APCs isolated from aa‐fed mice were unable to stimulate a Th1 response in vitro. Both phenotypic features of T cells from aa‐fed mice and their ability to produce a Th1 response in the presence of mature APCs were unaffected when compared with T cells from control mice. The results presented here support the notion that regulation of Th1 immunity to infection includes environmental factors such as dietary proteins, which provide a natural source of stimulation that contributes to the process of maturation of APCs.

show abstract

Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major.

Cited by 280 publications

References 65 publications

Experimental Infection of Balb/c Mice with Leishmania panamensis and Leishmania mexicana: Induction of Early IFN‐γ but not IL‐4 is Associated with the Development of Cutaneous Lesions

Experimental Infection of Balb/c Mice with Leishmania panamensis and Leishmania mexicana: Induction of Early IFN‐γ but not IL‐4 is Associated with the Development of Cutaneous Lesions

M-1/M-2 Macrophages and the Th1/Th2 Paradigm

Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice

Contact Info

Product

Resources

About