PD1, are augmented on monocytes/macrophages and T cells
during HIV-1 infection, suggesting dampening of the HIV-
speciﬁc effector T-cell function [32, 43, 44]. Although IL-21–
T cells have been associated with retroviral
control by affecting CD8
T lymphocytes in patients with a
low viral load , in immunocompromised hosts, IL-21 may
deﬂect innate and adaptive protective imm une responses
by inducing SOCS and CD274 expression. In addition, the
PD-1/PD-L1/PD-L2 pathway has been connected to sup-
pression of effector T-cell function against Mycobacterium
Although appropriate levels of IL-17 are thought to have a
protective role in response to infection, especially during the
early stages of infection with HIV-1 and M. tuberculosis, per-
sistent IL-17 is also associated with tissue-damaging inﬂam-
mation and negative outcomes [22, 47]. For instance, IL-17
has been reported to have immunopathological roles during
infection with multidrug-resistant M. tuberculosis and persis-
tently elevated levels of antigen . IL-17 contributes to the
pathogenesis of autoimmune/inﬂammatory conditions such
as rheumatoid arthritis, systemic lupus erythematosis, multiple
sclerosis, Sjögren syndrome, asthma, and Crohn disease
[15, 22]. IL-17 in CD68
monocytes/macrophages found in in-
ﬂamed mucosa of patients with inﬂammatory bowel disease
has been linked to induction and persistence of mucosal in-
ﬂammation . Recently, tissue macrophages expressing IL-17
have been described in breast tumors, where they promote
MAC regulates multiple host molecules in macrophages in
vitro, corresponding to evidence of their dysregulation in vivo
[13, 18]. Here, we exposed a new strategy used by this opportu-
nistic pathogen to promote persistence within the macrophage.
It is possible that, initially, IL-17 production by MAC-infected
macrophages may aid in recruiting cells and thereby mediate
resistance/protection activities that are important during the
early innate immune response. In immunocompromised indi-
viduals and during advanced disease, dysregulated production
of IL-17 in the absence of Th1 lymphocytes, IFN-γ, or ap-
propriate counterregulatory mechanisms to disengage IL-17
responses could drive pathogenesis.
Acknowledgments. We are grateful to Dr Ke-jian Lei, Wenwen Jin,
and Vichit Lorn, for technical assistance; to Calley Grace, for editorial
assistance; and Drs Alfredo Molinolo and Ramiro Iglesias-Bartolome, for
help with immunoﬂourescence staining of tissue.
Financial support. This work was supported by the Intramural
Research Program of the National Institute of Dental and Craniofacial
Potential conﬂicts of interests. All authors: No reported conﬂicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conﬂicts of Interest. Conﬂicts that the editors consider relevant to the
content of the manuscript have been disclosed.
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