Abstract:
:The P8 proteoglycolipid complex (P8 PGLC) is a glyconjugate expressed by Leishmania mexicana complex parasites. We previously have shown that vaccination with P8 PGLC provides protection against cutaneous leishmaniasis in susceptible BALB/c mice. However, the biological importance of this complex remains unknown. Here we show that P8 PGLC localizes to the surface of Leishmania pifanoi amastigotes and that upon exposure to macrophages, P8 PGLC binds and induces inflammatory cytokine and chemokine mRNAs such as tumor necrosis factor alpha and RANTES early after stimulation. Our studies indicate that cytokine and chemokine induction is dependent upon Toll-like receptor 4 (TLR4). Interestingly, key inflammatory cytokines and chemokines (such as interleukin-6 [IL-6], macrophage inflammatory protein 1beta, and beta interferon [IFN-beta]) that can be induced through TLR4 activation were not induced or only slightly upregulated by P8 PGLC. Activation by P8 PGLC does not occur in the presence of TLR4 alone and requires both CD14 and myeloid differentiation protein 2 for signaling; this requirement may be responsible for the limited TLR4 response. This is the first characterization of a TLR4 ligand for Leishmania. In vitro experiments indicate that L. pifanoi amastigotes induce lower levels of cytokines in macrophages in the absence of TLR4; however, notably higher IL-10/IFN-gamma ratios were found for TLR4-deficient mice than for BALB/c mice. Further, increased levels of parasites persist in BALB/c mice deficient in TLR4. Taken together, these results suggest that TLR4 recognition of Leishmania pifanoi amastigotes is important for the control of infection and that this is mediated, in part, through the P8 PGLC.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Whitaker SM,Colmenares M,Pestana KG,McMahon-Pratt Ddoi
10.1128/IAI.01528-07subject
Has Abstractpub_date
2008-05-01 00:00:00pages
2149-56issue
5eissn
0019-9567issn
1098-5522pii
IAI.01528-07journal_volume
76pub_type
杂志文章abstract::Colostrum was collected and pooled from each of five cows in three experimental groups: group I cows received intramuscular and intramammary inoculations of adjuvanted modified live Ohio Agricultural Research and Development Center rotavirus vaccine; group II cows were injected intramuscularly with a commercial modifi...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.41.3.1118-1131.1983
更新日期:1983-09-01 00:00:00
abstract::Group A streptococci isolated from skin adhere in greater numbers to human skin epithelial cells than to cells obtained from buccal mucosa whereas streptococci isolated from a throat tend to adhere in greater numbers to buccal epithelial cells than to skin epithelial cells in vitro. M protein-producing strains of grou...
journal_title:Infection and immunity
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doi:10.1128/IAI.18.2.555-557.1977
更新日期:1977-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00701-07
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.35.1.296-304.1982
更新日期:1982-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.41.3.1252-1260.1983
更新日期:1983-09-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.65.9.3768-3773.1997
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.8.3485-3493.1994
更新日期:1994-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.1.263-265.1987
更新日期:1987-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.16.1.263-267.1977
更新日期:1977-04-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.6.2920-2927.1999
更新日期:1999-06-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.31.1.487-494.1981
更新日期:1981-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.2.700-707.1999
更新日期:1999-02-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.00007-06
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.8.5204-5207.2005
更新日期:2005-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00617-19
更新日期:2019-11-18 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01237-10
更新日期:2011-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.37.1.209-215.1982
更新日期:1982-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.2.504-511.1993
更新日期:1993-02-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00911-12
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.70.6.2758-2762.2002
更新日期:2002-06-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.5.2319-2326.1999
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.74.1.265-272.2006
更新日期:2006-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.18.1.183-188.1977
更新日期:1977-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.52.1.323-325.1986
更新日期:1986-04-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.14.2.355-362.1976
更新日期:1976-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00542-17
更新日期:2018-02-20 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.7.1558-1563.1987
更新日期:1987-07-01 00:00:00