Heterozygosity for CCR5‐DΔ32 but not CCR2b‐64I protects against certain intracellular pathogens

Abstract

Results from this study show that heterozygosity for CCR5-Delta32 but not CCR2b-64I appears to protect against opportunistic infections.

Two-Year Safety and Virologic Efficacy of Maraviroc in Treatment-Experienced Patients With CCR5-Tropic HIV-1 Infection: 96-Week Combined Analysis of MOTIVATE 1 and 2

“…Of note, the delta 32 deletion of the CCR5 gene in humans has been associated with protective sequelae such as a reduced incidence of rheumatoid arthritis and delayed progression of hepatitis C. 14–17 Among HIV-infected individuals, the delta 32 deletion has been associated with reduced HIV disease progression and reduced risks of acquiring non-Hodgkin lymphoma and opportunistic infections such as toxoplasmosis, Pneumocystis jiroveci pneumonia, Mycobacterium avium complex, and cryptosporidiosis. 18–22 On the other hand, this mutation has also been associated with deleterious outcomes, including more severe West Nile virus and yellow fever virus infections. 23–25 To date, no such deleterious consequences have been seen with the long-term use of maraviroc in randomized controlled clinical studies.…”

Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination

“…CCR5 knockout mice clear Mycobacterium tuberculosis (Mtb) infection better compared with wild-type mice, during the early stages of infection these mice have increased numbers of lymphocytes in the lung and augmented inflammation [35]. Moreover, acquired immunodeficiency syndrome (AIDS) patients that are heterozygous for the CCR5⌬32 mutation seem to be protected against opportunistic infections with several pathogens including Mycobacterium avium, compatible with the notion that reduced immune regulation via CCL4/CCR5 can improve control of infection at least in (myco)bacterial infections [36]. CCR5⌬32 mutations have also been studied in the context of chronic hepatitis C infection (HCV) and indeed the frequency of homozygous mutants was increased among patients with HCV infection [37].…”

CC-Type chemokine receptor 5-Δ32 mutation protects against primary sclerosing cholangitis

“…In contrast, the Δ32 variant is found in only 1% of individuals of African origin and is absent in Asians 6,7. CCR5‐Δ32 heterozygosity is known to protect against internalization of pathogens such as HIV‐1 and other intracellular organisms such as mycobacteria, Pneumocystis jiroveci , and toxoplasma 5,8,9. The CCR5‐Δ32 variant also seems to be involved in the pathophysiology of a number of autoinflammatory diseases.…”