The tragic fate of group 3 innate lymphoid cells during HIV-1 infection
Xiaohuan Guo, Yang-Xin Fu
Xiaohuan Guo, Yang-Xin Fu
View: Text | PDF | Corrigendum
Commentary

The tragic fate of group 3 innate lymphoid cells during HIV-1 infection

Abstract

HIV-1 infection usually leads to systemic chronic inflammation that is associated with gut microbial translocation. The recently defined group 3 innate lymphoid cells (ILC3s) are critical for maintenance of intestinal barrier function; however, it is not clear whether and how HIV-1 infection influences the function of these cells. In this issue of the JCI, Zhang and colleagues present compelling evidence that the survival and function of ILC3s are dramatically impaired by HIV-1 infection. The authors provide evidence that HIV-1 infection induces persistent activation of plasmacytoid dendritic cells (pDCs) and production of type I IFNs, which together increase expression of death receptor CD95 on ILC3s and thereby promote subsequent ILC3 apoptosis. Together, these results identify a mechanism that explains the impaired intestinal barrier function that results from chronic HIV-1 infection and shed light on the role of pDCs in HIV-1 immunopathogenesis and therapy.

Authors

Xiaohuan Guo, Yang-Xin Fu

×

Figure 1

pDCs contribute to HIV-1–induced ILC3 dysfunction and depletion.

Options: View larger image (or click on image) Download as PowerPoint
pDCs contribute to HIV-1–induced ILC3 dysfunction and depletion. HIV-1 i...
HIV-1 infects and activates pDCs, which produce high levels of IFN-I within lymph tissues. While increased IFN-I upregulates CD95 expression and sensitizes tissue-resident ILC3s to CD95/FasL-mediated apoptosis, it also partially impairs IL-17a and IL-22 production by gut ILC3s. Thus, the numeral and functional impairment of ILC3s may lead to the loss of intestinal epithelial integrity, resulting in the release of bacteria and their products, such as LPS, into blood that in turn induce systematic activation. However, three key questions require future study: (a) What is the role of IFN-I in the induction of ILC3 apoptosis in vivo? (b) Do pDCs produce other cytokines involved in the regulation of ILC3? (c) How do human ILC3s protect against mucosal bacterial infections and maintain the mucosal barrier? The resolution of these issues will help determine whether strategies aimed to modulate ILC3 responses have therapeutic potential to benefit patients with chronic HIV-1.