38-C 7 JANUARY 2022 • VOL 375 ISSUE 6576 science.org SCIENCE
RESEARCH | IN SCIENCE JOURNALS
and even death in humans.
Disease occurrence is linked to
the geographic range of the tick
vector, and climate change may
increase this range. Infection
of host cells requires the
fusion glycoprotein Gc, which
is the main target of neutral-
izing antibodies. Mishra et al.
build on previous work that
identified a combination of two
Gc-targeting antibodies that
gave postexposure protection
in an animal model. The authors
determined the structure of the
antigen-binding fragments of
the two antibodies bound to a
prefusion form of Gc and also
the structure of Gc after the
conformational change into the
trimeric postfusion form. The
structures show how the anti-
bodies work together to block
membrane fusion. —VV
Science, abl6502, this issue p. 104
NITROGEN CYCLE
Consuming oxygen,
but making it too
For marine microbes, there
are myriad biological reac-
tions involved in the cycling of
nutrients and the generation of
energy. Availability of oxygen is
crucial for many species’ metab-
olism. Kraft et al. were surprised
to find that pure cultures of an
ammonia-oxidizing archaean
(AOA) (see the Perspective by
Martens-Habbena and Qin),
Nitosopumilus maritimus,
were able to regenerate small
amounts of oxygen when
placed under anoxic conditions.
Isotope labeling of nitrogen
species revealed a series of
reactions transforming nitrite,
the expected metabolic end
product, into nitric oxide, nitrous
oxide, and, eventually, dinitrogen.
Oxygen was also formed, likely
from nitric oxide disproportion-
ation, but was mostly consumed,
which is consistent with the
overall aerobic metabolism of
AOA. These organisms can be
found in oxygen-depleted waters
and may benefit from producing
oxygen from nitrite under these
conditions. —MAF
Science, abe6733, this issue p. 97;
see also abn0373, p. 27
INFLAMMATION
Complement coordination
in macrophages
The serum complement system
performs well-established func-
tions in innate immune system
recognition and destruction of
invading pathogens, but comple-
ment proteins produced by
immune cells can also execute
distinct functions intracellu-
larly. In human macrophages,
Niyonzima et al. demonstrated
that the complement protein
C5a signals on mitochondrial
membranes through its receptor,
C5aR1, to control interleukin-1B
(IL-1B) production in response
to cholesterol crystal uptake.
C5a–C5aR1 signaling altered
mitochondrial activity and
increased reactive oxygen
species production, promot-
ing IL-1B gene expression and
processing. In a mouse model
of atherosclerosis in which
cholesterol crystal accumulates
in arterial walls, deletion of
C5aR1 in myeloid cells reduced
the severity of cardiovascular
disease. These results identify a
function for intracellular comple-
ment proteins in myeloid cell
mitochondrial metabolism and
response to sterile inflamma-
tion. —CO
Sci. Immunol. 6 , eabf2489 (2021).CELL AND GENE THERAPY
Making CAR T cells in vivo
Cardiac fibrosis, the stiffening
and scarring of heart tissue, can
be fatal. Rurik et al. designed an
immunotherapy strategy to gen-
erate transient chimeric antigen
receptor (CAR) T cells that can
recognize the fibrotic cells in
the heart (see the Perspective
by Gao and Chen). By injecting
CD5-targeted lipid nanoparticles
containing the messenger RNA
(mRNA) instructions needed
to reprogram T lymphocytes,
the researchers were able to
generate therapeutic CAR T cells
entirely inside the body. Analysis
of a mouse model of heart dis-
ease revealed that the approach
was successful in reducing fibro-
sis and restoring cardiac function.
The ability to produce CAR T cells
in vivo using modified mRNA mayhave a number of therapeutic
applications. —PNK
Science, abm0594, this issue p. 91;
see also abn0851, p. 23PALEOECOLOGY
Species shifts
Our anthropogenically warmed
climate will lead to a suite of
organismal changes. To predict
how some of these may occur, we
can look to past warm (inter-
glacial) periods. Salvatteci et al.
used this approach and looked at
a marine sediment record of the
Humboldt Current system off the
coast of Peru (see the Perspective
by Yasuhara and Deutsch).
They found that previous warm
periods were dominated by small,
goby-like fishes, whereas this
ecosystem currently is dominated
by anchovy-like fishes. Such a
shift is not only relevant to eco-
system shifts but also to fisheries
because anchovies are heav-
ily fished as a food source and
gobies are much less palatable
than anchovies. —SNV
Science, abj0270, this issue p. 101;
see also abn2384, p. 25NEUROINFLAMMATION
Denying entry
Blocking infiltration of patho-
genic immune cells into the
central nervous system (CNS)
can prevent autoimmune
neuroinflammation. However,
selectively targeting pathogenic
cells while still allowing the
infiltration of protective cells has
proved challenging. Charabati
et al. identified dual immuno-
globulin domain–containing cell
adhesion molecule (DICAM)
as a mediator of pathogenic, T
helper 17 (TH17) cell trafficking
into the CNS. DICAM was highly
expressed on TH17 cells isolated
from patients with multiple scle-
rosis. Blockade of DICAM with
an antibody in mice prevented
TH17 cell infiltration, reduc-
ing disease severity in models
of experimental autoimmune
encephalomyelitis, suggesting
that DICAM merits further explo-
ration as a therapeutic target for
neuroinflammation. —CSM
Sci. Transl. Med. 13 , eabj0473 (2022).