INSIGHTS | PERSPECTIVES
sciencemag.org SCIENCEof blue carbon in coastal ecosystems makes
substantial contributions to the mitigation
of global climate change ( 12 ).
Without sufficient sediment and root
growth to reduce the impacts of SLR, man-
grove cover might be sustained through
landward migration of mangroves onto
floodplains. This would increase carbon
sequestration, but landward retreat is com-
plex and can be costly for governments and
landholders ( 13 ). The threshold provided by
Saintilan et al., combined with knowledge
of local factors that influence relative SLR,
provides opportunities to develop time lines
for decisions and actions that will maintain
mangroves in the land-seascape.
There are caveats to consider in the new
study. Over the late Holocene, rates of SLR
were mostly declining, whereas Earth cur-
rently faces accelerating SLR, which might
alter the threshold. There could be lags in
responses of mangrove cover to relative SLR
that exceed the 6- to 7-mm/year threshold,
and lags can vary with species traits and dis-
turbance regimens, such as frequency and
intensity of storms that exacerbate the im-
pacts of SLR and which are predicted to in-
tensify with climate change in many regions.
Nevertheless, providing an evidence-based
relative SLR threshold for mangrove survival
can help stimulate solutions for coastal man-
agement. If nations and communities wish
to harness the potential of blue carbon to
mitigate climate change and to protect mil-
lions of people who depend on mangroves
for shelter, flood protection, food, and fiber,
then solutions for staying below the 6- to
7-mm/year relative SLR threshold should
be the goal of civil society and governments.
With reduction in CO 2 emissions, equitable
management of river water and sediment
flows, limitations in water and oil extraction
on floodplains, and conservation and plan-
ning for landward migration, mangroves can
be maintained into the future. j
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- Intergovernmental Panel on Climate Change (IPCC),
“Climate Change 2013: The Physical Science Basis.
Working Group 1 Contribution to the Fifth Assessment
Report of the Intergovernmental Panel on Climate
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(2018). - M. Becker et al., Proc. Natl. Acad. Sci. U.S.A. 117 , 1867
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(2017).
10.1126/science.abc3735IMMUNOLOGYThe specifics of innate
immune memory
Innate immune cells develop specific memory
involved in transplant rejection in mice
By Jorge Domínguez-Andrés^1
and Mihai G. Netea1,2O
ne of the most important traits of
immune host defense against patho-
gens is memory, which improves
survival if the same pathogen is
reencountered. However, immune
memory can also be deleterious, driv-
ing autoimmune diseases and the rejection
of transplanted organs. Memory character-
istics have been considered a fundamental
property of adaptive immune cells such as T
and B lymphocytes ( 1 ). However, innate im-
mune cells such as myeloid cells and natural
killer (NK) cells can also adapt to previous
encounters with pathogens through epigen-
etic, transcriptional, and functional repro-
gramming, called trained immunity ( 2 ). The
discovery of this innate immune memory
emerged from studies with live vaccines
and was described as being largely nonspe-
cific ( 3 ). On page 1122 of this issue, Dai et al.
( 4 ) reveal that monocytes and macrophages
acquire specific memory and induce organ
rejection in mice, which could be prevented
to improve transplantation outcomes.
Dai et al. use a series of elegant transplant
models in different mouse strains, showing
that the rejection of grafts is maintained in
individuals without a functional adaptive im-
mune response. Graft rejection was mediated
by monocytes and macrophages, which re-
tained their memory functions several weeks
after the encounter with antigens from the
donor. This specific memory response was
dependent on paired immunoglobulin-like
receptor-A (PIR-A), an activation receptor ex-
pressed by B cells and myeloid lineage cells,
which can recognize major histocompatibil-
ity complex class I (MHC-I) molecules (see
the figure). MHC-I expressed on the surface
of most nucleated cells presents peptide frag-
ments of endogenous proteins, which can be
subsequently recognized as antigens by the
immune cells of the recipient of a transplant
and cause its rejection ( 5 ). Blocking or delet-ing PIR-A receptors impaired the recognition
of MHC-I–peptide complexes expressed in
the donor cells, which decreased the rejec-
tion of transplanted hearts and kidneys and
improved outcomes.
This specificity of innate immune mem-
ory in mouse myeloid cells described by
Dai et al. is reminiscent of memory char-
acteristics of innate immune cells of sev-
eral invertebrates, which lack an adaptive
immune system. These include diversifica-
tion of genes encoding fibrinogen-related
proteins (FREPs) in mollusks ( 6 ) and scav-
enger receptor cysteine-rich proteins in
echinoderms ( 7 ) or alternative splicing of
the immunoglobulin (Ig) domain–encoding
gene Down syndrome cell adhesion mol-
ecule (Dscam) in insects ( 5 ). It is important
to note that in both vertebrates and inver-
tebrates, the Ig superfamily of molecules is
often the pillar mediating specificity of the
innate immune memory responses. Indeed,
PIR-A, B cell receptors, immunoglobulins,
and T cell receptors share a similar type of
structure, which argues for an evolutionary
continuum of memory specificity in innate
and adaptive immune responses.
Ig-based specific immune responses
complement the more primitive nonspecific
trained immunity-mediated memory ( 8 ).
The increased responsiveness provided by
trained immunity after certain infections or
vaccinations can induce protection against
both specific and heterologous infections
( 9 , 10 ). Yet, in conditions characterized by
excessive immune responses, such as in-
flammatory and autoimmune diseases and
organ transplant rejection, enhanced innate
immune responses can aggravate the patho-
logical consequences of inflammation. It is
crucial to know the roles played by innate
immune cells in transplant rejection, in or-
der to target it and improve survival.
The findings of Dai et al. have several im-
plications that go beyond transplantation.
If monocytes and macrophages can develop
specific memory to MHC-I–presented anti-
gens, this reveals possible therapeutic ap-
proaches in organ transplantation, but also
autoimmune and inflammatory diseases.
In addition, it is intriguing to hypothesize
whether specific innate immune memory(^1) Department of Internal Medicine and Radboud Center for
Infectious Diseases, Radboud, Netherlands.^2 Immunology and
Metabolism, Life and Medical Sciences Institute, University of
Bonn, Bonn, Germany. Email: [email protected]
1052 5 JUNE 2020 • VOL 368 ISSUE 6495
Published by AAAS