Journal of Immunology Research / 2017 / Article / Tab 1

Review Article

Getting “Inside” Type I IFNs: Type I IFNs in Intracellular Bacterial Infections

Table 1

Mechanisms of type I IFN induction by intracellular bacteria and downstream consequences of induction. Type I IFNs are induced via various signaling pathways depending on the bacterial ligand and host cell type. Repercussions of type I IFN production differ between intracellular bacteria, cell type infected, and model/route of infection among other factors.

BacteriaGram stainInduction of type I IFNRole of type I IFNEffects on hostReferences

C. trachomatis/muridarumcGAS generates cGAMP from Chlamydial
DNA which activates STING/IRF3
(1) Beneficial(1) Depletes intracellular iron and regulates
IDO which can alter tryptophan availability
to bacteria; IFN-α together with IFN-γ or
TNF-α has synergistic antichlamydial effect
[44, 7173]
(2) Detrimental(2) Decreased chlamydia-specific T cells and
decreased CXCL9-induced T cell
recruitment prevent bacterial clearance

L. monocytogenes+DNA- or CDN-mediated signaling via
IFI16 and STING, RNA signaling via RIG-I
or MDA5, RNA Pol III transcription of DNA
to RNA, NOD2 detection of MDP in
conjunction with cytosolic detection of DNA
(1) Beneficial(1) Decreases inflammatory pathology in
liver and induces rapid protective cytokine
response after intragastric infection
[43, 49, 74, 7984,
8789, 9193, 95]
(2) Detrimental(2) Increases expression of apoptotic genes
and increases apoptosis of lymphocytes and
macrophages needed for bacterial clearance,
decreases production of antibacterial
IL-12p70, and decreases TNF-α secretion
from macrophages; dampened macrophage
responsiveness to IFN-γ makes these cells
more permissive to infection/replication,
decreases numbers of IL-17A-secreting
γδ T cells thereby decreasing neutrophil
recruitment and bacterial control in the
spleen, increases cell-to-cell spread of
bacteria, and inhibits CD8 T cell priming

M. tuberculosisNAcGAS-dependent generation of CDNs
which activate STING, NOD2 detects
Mycobacterial MDP leading to activation
of RIP2 and IRF5
(1) Beneficial(1) Hypervirulent strain promotes alternative
macrophage activation in the absence
of IFN-γ that controls bacterial replication
[20, 41, 42, 98, 105107]
(2) Detrimental(2) Dampens antibacterial IL-1β production,
IL-10 downstream of type I IFNs reduces
antibacterial activity of IFN-γ; causes
fatal inflammation due to increased
chemokine production, neutrophil
recruitment to the lung, and alveolar
macrophage death

S. enterica serovar
TRIF-dependent TLR3 and TLR4 signaling
likely via nucleic acids and LPS, respectively,
RIG-I detection of RNA
(1) Beneficial(1) Important for antibacterial macrophage
[111114, 118,
120122, 124]
(2) Detrimental(2) Increased caspase-11-mediated
macrophage death allowing bacterial
release which is exacerbated in the
absence of caspase-1, a protein required
for neutrophilic control of infection, increases
RIP1/RIP3-mediated macrophage death;
suppresses IL-1 cytokine and neutrophil
chemoattractant transcripts in macrophages
which decreases bacterial control;
influenza-induced type I IFNs negatively
impact gut microbiota and decrease innate
responses in the gut, increasing
susceptibility to S. enterica

F. tularensiscGAS, IFI204, STING, and IRF3-dependent(1) Beneficial(1) Type I IFN-induced GBPs activate AIM2
inflammasome leading to macrophage
pyroptosis and removal of
replicative niche
[91, 126, 135139]
(2) Detrimental(2) Decreased number of IL-17A-secreting
γδ T cells which are important for
neutrophil recruitment to the spleen
and bacterial control

B. abortusRNA Pol III and/or STING are
required for type I IFN induction in a
MyD88-dependent but TRIF-
and TLR-independent manner
(1) Detrimental(1) Alters DC maturation which dampens
DC cytokine production; increases bacterial
load due to decreases in IFN-γ and NO
production; increases splenocyte
apoptosis and Trail expression in
[36, 141, 144]

L. pneumophilaRIG-I detection of RNA and subsequent
signaling through IPS-1 and IRF3, RNA
Pol III-dependent transcription of DNA to
RNA then signaling via RIG-I and IPS-1,
CDN detection via STING
(1) Beneficial(1) Controls bacterial replication within host
cell vacuoles; promotes inflammatory
macrophage polarization and
bacterial clearance
[47, 82, 150154]

C. burnetiiNOD1/2, RIG-I, and/or TLR7/9-mediated
production of IFN- α in pDCs, involves IRF7
(1) Beneficial(1) Administration to lung was
protective—mechanism unknown at
this time
[167, 169]
(2) Detrimental(2) Lack of IFNAR benefited host; i.p.
delivery of IFN-α was harmful to host
perhaps due to suppression of necessary
inflammatory cytokines

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