Track topics on Twitter Track topics that are important to you
Effective resolution of malaria infection by avoiding pathogenesis requires regulated pro- to anti-inflammatory responses and the development of protective immunity. TLRs are known to be critical for initiating innate immune responses, but their roles in the regulation of immune responses and development of protective immunity to malaria remain poorly understood. In this study, using wild-type, TLR2(-/-), TLR4(-/-), TLR9(-/-), and MyD88(-/-) mice infected with Plasmodium yoelii, we show that TLR9 and MyD88 regulate pro/anti-inflammatory cytokines, Th1/Th2 development, and cellular and humoral responses. Dendritic cells from TLR9(-/-) and MyD88(-/-) mice produced significantly lower levels of proinflammatory cytokines and higher levels of anti-inflammatory cytokines than dendritic cells from wild-type mice. NK and CD8(+) T cells from TLR9(-/-) and MyD88(-/-) mice showed markedly impaired cytotoxic activity. Furthermore, mice deficient in TLR9 and MyD88 showed higher Th2-type and lower Th1-type IgGs. Consequently, TLR9(-/-) and MyD88(-/-) mice exhibited compromised ability to control parasitemia and were susceptible to death. Our data also show that TLR9 and MyD88 distinctively regulate immune responses to malaria infection. TLR9(-/-) but not MyD88(-/-) mice produced significant levels of both pro- and anti-inflammatory cytokines, including IL-1β and IL-18, by other TLRs/inflammasome- and/or IL-1R/IL-18R-mediated signaling. Thus, whereas MyD88(-/-) mice completely lacked cell-mediated immunity, TLR9(-/-) mice showed low levels of cell-mediated immunity and were slightly more resistant to malaria infection than MyD88(-/-) mice. Overall, our findings demonstrate that TLR9 and MyD88 play central roles in the immune regulation and development of protective immunity to malaria, and have implications in understanding immune responses to other pathogens.
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033.
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
Soaring rates of systemic fungal infections worldwide underscore the need for vaccine prevention. An understanding of the elements that promote vaccine immunity is essential. We previously reported th...
Pregnancy-associated malaria, including placental malaria, causes significant morbidity and mortality worldwide. Recently, it has been suggested that in utero exposure of the fetus to malaria antigens...
With increasing malaria control and goals of malaria elimination, many endemic areas are transitioning from high-to-low-to-no malaria transmission. Reductions in transmission will impact on the develo...
How early interactions between innate and adaptive immune cells influence outcomes of acute infections is incompletely understood. In this issue of Immunity, Karunarathne et al. (2016) show that dend...
Accumulating evidence indicates that inflammatory signals required for maximizing effector T cell generation have opposing effects on the development of memory T cell precursors. Toll-like receptor (T...
The overall objective is to evaluate the effect of exposure to Plasmodium (P.) falciparum erythrocytic stage antigens during different periods of infancy on the development of naturally ac...
The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States
Plasmodium falciparum malaria remains a global public health threat. Leading malaria vaccine candidates confer only partial short-lived protection at best. An understanding of the mechanis...
This study aims to assess the safety and effectiveness of four new candidate malaria vaccines; ChAd63 CS, ChAd63 ME-TRAP, MVA CS & MVA ME-TRAP. These vaccines consist of viruses (ChAd63 an...
This phase Ib/II trial studies the side effects and best dose of toll-like receptor 9 (TLR9) agonist SD-101 when given together with ibrutinib and radiation therapy and to see how well the...
Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.
Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.
A biguanide compound which has little antimalarial activity until metabolized in the body to the active antimalarial agent cycloguanil. The usefulness of proguanil is limited by the rapid development of drug resistance by the malarial parasite. The hydrochloride is used for the casual prophylaxis of falciparum malaria, to suppress other forms of malaria, and to reduce transmission of infection (From Martindale, The Extra Pharmacopoeia, 30th ed, p405)
A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...