| Title |
Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection
|
|---|---|
| Published in |
Nature Immunology, December 2011
|
| DOI | 10.1038/ni.2180 |
| Pubmed ID | |
| Authors | |
| Abstract |
Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 50% |
| United States | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 6 | 2% |
| France | 4 | 1% |
| United Kingdom | 2 | <1% |
| Brazil | 2 | <1% |
| Singapore | 1 | <1% |
| Sweden | 1 | <1% |
| Portugal | 1 | <1% |
| Peru | 1 | <1% |
| Korea, Republic of | 1 | <1% |
| Other | 3 | <1% |
| Unknown | 376 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 95 | 24% |
| Researcher | 83 | 21% |
| Student > Master | 50 | 13% |
| Student > Bachelor | 35 | 9% |
| Student > Doctoral Student | 23 | 6% |
| Other | 48 | 12% |
| Unknown | 64 | 16% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 124 | 31% |
| Immunology and Microbiology | 89 | 22% |
| Medicine and Dentistry | 45 | 11% |
| Biochemistry, Genetics and Molecular Biology | 42 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 7 | 2% |
| Other | 20 | 5% |
| Unknown | 71 | 18% |