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Curr Opin Immunol. 2017 Oct;48:122-133. doi: 10.1016/j.coi.2017.09.002. Epub 2017 Oct 6.

Pathogenesis of infections in HIV-infected individuals: insights from primary immunodeficiencies.

Author information

1
Sidra Medical and Research Center, Doha, Qatar. Electronic address: qzhang@sidra.org.
2
Department of Clinical Microbiology, Hôpital Necker Enfants Malades, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France; Pediatric Hematology and Immunology Unit, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
3
Pediatric Hematology and Immunology Unit, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
4
Pediatric Hematology and Immunology Unit, Hôpital Necker Enfants Malades, AP-HP, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Hôpital Necker Enfants Malades, Paris, France; Paris Descartes University, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, New York, NY, USA.

Abstract

Following infection with almost any given microorganism other than an emerging pathogen, only a minority of individuals develop life-threatening clinical disease, implying that these individuals have some form of immunodeficiency. A growing number of inherited and acquired immunodeficiencies have been deciphered over the last 50 years. HIV infection is probably the best-known acquired immunodeficiency. It emerged about 40 years ago and precipitates various severe infections, the occurrence of which is associated with a fall in circulating CD4+ T cells. However, despite the strength of this correlation, infection rates differ between patients with similar levels and durations of CD4+ T lymphopenia in the presence or absence of antiretroviral treatment. Moreover, a few infections seem to be less dependent on total CD4+ T-cell levels. The fine detail of the mechanisms underlying these infections is unknown. We discuss here how studies of the human genetics and immunology of some of these infections in patients with primary immunodeficiencies (PIDs) have provided unique insights into their molecular and cellular basis. Defects of specific CD4+ Th-cell subsets account for some of these infections, as best exemplified by Th1* for mycobacteriosis and Th17 for candidiasis. PIDs are individually rare, but collectively much more common than initially thought, with new disorders being discovered at an ever-increasing pace and a global prevalence worldwide approaching that of HIV infection. Studies of known and new PIDs should make it possible to dissect the pathogenesis of most human infections at an unprecedented level of molecular and cellular precision. The predictive, preventive, and therapeutic implications of studies of immunity to infection in PIDs may extend to HIV-infected patients and patients with infectious diseases in other settings.

PMID:
28992464
PMCID:
PMC5682227
DOI:
10.1016/j.coi.2017.09.002
[Indexed for MEDLINE]
Free PMC Article

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