Simian Immunodeficiency Virus Infection Induces Expansion of α4β7⁺and Cytotoxic CD56⁺NK Cells

Abstract

Herein we demonstrate that chronic simian immunodeficiency virus (SIV) infection induces significant upregulation of the gut-homing marker ␣4␤7 on macaque NK cells, coupled with downregulation of the lymph node-trafficking marker, CCR7. Interestingly, in naïve animals, ␣4␤7 expression was associated with increased NK cell activation and, on CD16 ؉ NK cells, delineated a unique dual-function cytotoxic-CD107a ؉ /gamma interferon (IFN-␥)-secreting population. However, while SIV infection increased CD107a expression on stimulated CD56؉ NK cells, ␣4␤7 ؉ and ␣4␤7 ؊ NK cells were affected similarly. These findings suggest that SIV infection redirects NK cells away from the lymph nodes to the gut mucosae but alters NK cell function independent of trafficking repertoires.

Accumulation of Cytotoxic CD16+NK Cells in Simian Immunodeficiency Virus-Infected Lymph Nodes Associated withIn SituDifferentiation and Functional Anergy

“…This result suggests that decreased trafficking to the LNs may in part account for the low frequency of LN NK cells during acute infection but does not inform the high frequency of CD16 ϩ NK cells observed in chronic infection. This agrees with previous findings that peripheral NK cells increase trafficking to the gut, not the LNs, during SIV infection (11).…”

“…ϩ NK cells become more prevalent in the periphery, while CD56 ϩ NK cells accumulate in the gut and acquire a more cytotoxic phenotype (11,12). In HIV infection, further viral replication causes the rise of abnormal CD56 Ϫ CD16 ϩ NK cells that are anergic, exhibiting low CD107a degranulation responses (10,13).…”

“…During acute HIV infection, the cytotoxic CD56 dim CD16 ϩ NK cell subset expands in peripheral blood mononuclear cells (PBMC), whereas cytokine-producing CD56 bright NK cells contract in this compartment (10). Likewise, in SIV infection of rhesus macaques, CD16 ϩ NK cells become more prevalent in the periphery, while CD56 ϩ NK cells accumulate in the gut and acquire a more cytotoxic phenotype (11,12). In HIV infection, further viral replication causes the rise of abnormal CD56 Ϫ CD16 ϩ NK cells that are anergic, exhibiting low CD107a degranulation responses (10, 13).…”

A Genetic Polymorphism of FREM1 Is Associated with Resistance against HIV Infection in the Pumwani Sex Worker Cohort

“…With two RGD (arginine-glycine-aspartic acid) and 12 CSPG (chondroitin sulfate proteoglycan) domains, FREM1 variants can potentially exert different functions by differentially interacting with integrin, collagen, and fibronectin through variations in functional domains (26). These are important components of the genital mucosal barrier and play an important role in HIV-1 infection (4,6,7,10,13,14,33,43,51). The C-type lectin and Calx-beta domain of FREM1 suggest the ability of this protein to bind sugar and calcium and modify biological function.…”

Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

“…This model has also highlighted the role of CD4þ T CM as main targets of the virus in vivo [27][28][29], as well as the dramatic and rapid depletion of CD4þ T cells in the gut [30], and has contributed to demonstrating that microbial translocation is associated with disease progression [31]. Finally, the macaque/SIVmac model has revealed the significant trafficking of immune cells, such as natural killer (NK) cells and plasmacytoid dendritic cells (pDCs), from the periphery to the gut mucosa during infection [32,33]. Trafficking to the gut was associated with upregulation of a4b7 on NK cells and pDCs and blocking of a4b7 could reduce viral loads in this tissue [34].…”