Effects Produced by the Intravenous Injection in Man of a Toxic Antigenic Material Derived From Eberthella Typhosa: Clinical, Hematological, Chemical and Serological Studies

Favorite, Grant O.; Morgan, Herbert R.

doi:10.1172/jci101337

Cited by 66 publications

(31 citation statements)

References 10 publications

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“…It has been known for quite a long time that exposure to TLR agonists leads to the development of tolerance through a blockade of the corresponding signal transduction pathways (38)(39)(40). Tolerance almost certainly occurs in patients from holoendemic areas of malaria that do not exhibit the signs and symptoms of the disease despite the presence of blood parasites (41,42).…”

Section: Discussionmentioning

confidence: 99%

IFN-γ–Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria

Silva

Salles

Panatieri

et al. 2013

The Journal of Immunology

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The mechanism by which protective immunity to Plasmodium is lost in the absence of continued exposure to this parasite has yet to be fully elucidated. It has been recently shown that IFN-γ produced during human and murine acute malaria primes the immune response to TLR agonists. In this study, we investigated whether IFN-γ–induced priming is important to maintain long-term protective immunity against Plasmodium chabaudi AS malaria. On day 60 postinfection, C57BL/6 mice still had chronic parasitemia and efficiently controlled homologous and heterologous (AJ strain) challenge. The spleens of chronic mice showed augmented numbers of effector/effector memory (TEM) CD4+ cells, which is associated with increased levels of IFN-γ–induced priming (i.e., high expression of IFN-inducible genes and TLR hyperresponsiveness). After parasite elimination, IFN-γ–induced priming was no longer detected and protective immunity to heterologous challenge was mostly lost with >70% mortality. Spontaneously cured mice had high serum levels of parasite-specific IgG, but effector T/TEM cell numbers, parasite-driven CD4+ T cell proliferation, and IFN-γ production were similar to noninfected controls. Remarkably, the priming of cured mice with low doses of IFN-γ rescued TLR hyperresponsiveness and the capacity to control heterologous challenge, increasing the TEM cell population and restoring the CD4+ T cell responses to parasites. Contribution of TLR signaling to the CD4+ T cell responses in chronic mice was supported by data obtained in mice lacking the MyD88 adaptor. These results indicate that IFN-γ–induced priming is required to maintain protective immunity against P. chabaudi and aid in establishing the molecular basis of strain-transcending immunity in human malaria.

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Section: Discussionmentioning

confidence: 99%

IFN-γ–Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria

Silva

Salles

Panatieri

et al. 2013

The Journal of Immunology

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show abstract

“…LPS-challenged humans, for example, are hyporesponsive to LPS-mediated responses when subsequently re-challenged (18). Cells from patients with Gramnegative bacterial septicemia are similarly hyporesponsive to LPS (19), indicating that the TLR4 pathway has entered into a state of innate immune ''tolerance'' (20).…”

mentioning

confidence: 99%

Malaria primes the innate immune response due to interferon-γ induced enhancement of toll-like receptor expression and function

Franklin

Parroche

Ataide

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

178

171

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“…; accepted March 7, 1963) Endotoxins prepared from gram-negative bacteria induce profound physiologic derangements in man (1), yet their clinical significance during illnesses induced by gram-negative bacteria is speculative. One major objection to ascribing any significant role to endotoxin in mediating the pathophysiologic changes of infection is based on the phenomenon of acquired tolerance.…”

mentioning

confidence: 99%

The Role of Endotoxin During Typhoid Fever and Tularemia in Man. I. Acquisition of Tolerance to Endotoxin*

Greisman¹,

Hornick²,

Carozza³

et al. 1963

J. Clin. Invest.

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Effects Produced by the Intravenous Injection in Man of a Toxic Antigenic Material Derived From Eberthella Typhosa: Clinical, Hematological, Chemical and Serological Studies

Cited by 66 publications

References 10 publications

IFN-γ–Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria

IFN-γ–Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria

Malaria primes the innate immune response due to interferon-γ induced enhancement of toll-like receptor expression and function

The Role of Endotoxin During Typhoid Fever and Tularemia in Man. I. Acquisition of Tolerance to Endotoxin*

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