case, they would decrease their pulse interval
and lower their end frequency even more than
we saw in our bats (see table S2). Because the
plate does not reflect any echoes toward the bat
until the bat is next to it, we suggest that they
considered it to be an opening in the wall and
intended to escape the room through this apparent, constrained flyway (21, 22).
In the horizontal setup, bats never collided
with but carefully approached the surface to
drink. Thus, they demonstrate an orientation-dependent interpretation of their ensonified
environment as the direction of the same cue
(the lack of echo from an area ahead) elicits a
different behavior. The change in amplitude of
the perpendicular echo from a rough to a smooth
surface might further give bats an orientational
cue (movie S3). If the perpendicular echo is perceived from below in combination with otherwise
missing echoes, bats interpret this as a water surface and can use it as a height estimator (9, 23).
Coming from the side, it warns them of an approaching obstacle in what they have until now
construed as a clear flight path, if they have had
enough time to process it. Bats have been found
to fly against smooth surfaces in the lab and the
field (14–16), but these observations were interpreted with a focus on visual influence and failed
to explain the underlying sensory mechanism
[however, see (16), pp. 51–52]. Furthermore, bats
have been found dead and injured next to human-made structures such as the glass facades of a
convention center or towers (17, 24–26).
We now understand that smooth, vertical surfaces demonstrate a possible acoustic sensory
trap for bats. Although none of our bats was hurt,
an often higher flight speed in natural settings
might lead to serious injuries such as concussions, broken wings, or broken jaws. Injured bats
are often only accounted for as a by-product of
investigations on avian mortality and furthermore might crawl away or fall prey to predators
(27), thus concealing and underestimating the
actual numbers of fatalities. For a better understanding of the actual impact on bats, increased
monitoring and systematic recording of collisions
at vertical mirror situations (such as big glass
surfaces) are required. Moreover, smooth, vertical surfaces should be avoided at crucial sites
such as “migratory highways,” key foraging
habitats, or bat colonies. And finally, mitigation
efforts such as ultrasonic bat deterrents could
be tested around selected human structures.
Only if we identify and evaluate the real extent
of collisions with acoustic mirrors can we avoid
or mitigate potential detrimental effects on bat
REFERENCES AND NOTES
1. M. A. Schlaepfer, M. C. Runge, P. W. Sherman, Trends Ecol.
Evol. 17, 474–480 (2002).
2. B. A. Robertson, R. L. Hutto, Ecology 87, 1075–1085 (2006).
3. R. J. Fletcher Jr., J. L. Orrock, B. A. Robertson, Proc. R. Soc. B
279, 2546–2552 (2012).
4. B. A. Robertson, J. S. Rehage, A. Sih, Trends Ecol. Evol. 28,
5. T. Longcore, C. Rich, Front. Ecol. Environ 2, 191–198 (2004).
6. G. Horváth, G. Kriska, P. P. Malik, B. Robertson, Front. Ecol.
Environ 7, 317–325 (2009).
7. C. L. Madliger, Biodivers. Conserv. 21, 3277–3286 (2012).
8. W. Halfwerk, H. Slabbekoorn, Biol. Lett. 11, 20141051 (2015).
9. S. Greif, B. M. Siemers, Nat. Commun. 1, 107 (2010).
10. S. Danilovich et al., Curr. Biol. 25, R1124–R1125 (2015).
11. H.-U. Schnitzler, E. K. V. Kalko, Bioscience 51, 557–569
12. H.-U. Schnitzler, C. F. Moss, A. Denzinger, Trends Ecol. Evol. 18,
13. C. F. Moss, A. Surlykke, Front. Behav. Neurosci. 4, 33
14. W. H. Davis, R. W. Barbour, Am. Midl. Nat. 74, 497–499
15. L. P. McGuire, M. B. Fenton, Acta Chiropt. 12, 247–250
16. R. W. Howard, Auritus: A Natural History of the Brown Long-Eared Bat (Ebor Press, York, UK, 1995).
17. See supplementary materials.
18. A. Surlykke, S. Boel Pedersen, L. Jakobsen, Proc. R. Soc. B
276, 853–860 (2009).
19. L. Jakobsen, J. M. Ratcliffe, A. Surlykke, Nature 493, 93–96
20. M. L. Melcón, H. U. Schnitzler, A. Denzinger, J. Comp. Physiol. A
195, 69–77 (2009).
21. A. E. Petrites, O. S. Eng, D. S. Mowlds, J. A. Simmons,
C. M. DeLong, J. Comp. Physiol. A 195, 603–617 (2009).
22. A. Surlykke, K. Ghose, C. F. Moss, J. Exp. Biol. 212, 1011–1020
23. S. Hoffmann et al., J. Neurophysiol. 113, 1135–1145 (2015).
24. R. G. Van Gelder, Trans. Kans. Acad. Sci. 59, 220–222 (1956).
25. R. L. Crawford, W. W. Baker, J. Mammal. 62, 651–652 (1981).
26. R. M. Timm, Bull. Chicago Acad. Sci. 14, 1–7 (1989).
27. M. M. P. Huso, Environmetrics 22, 318–329 (2011).
All experiments were carried out under license of the Bulgarian
authorities [Bulgarian Ministry of Environment and Water, and
Regional Inspectorate (RIOSV) Ruse, permits 193/01.04.2009
and 205/29.05.2009] and the Hungarian authorities [National
Inspectorate for Environment, Nature and Water (OKTVF) permit
14/5969/3/2011]. Supported by Human Frontier Science Program
grant RGP0062/2009 (B.M.S.); National Research, Development
and Innovation Office, Hungary (NKFIH) grant PD-115730
(S.Z.); the Minerva Foundation (S.G.); and the Max Planck
Society. The authors report no conflict of interest. All
data used in statistics are archived at the Edmond Data
Repository ( http://edmond.mpdl.mpg.de/imeji/collection/
Materials and Methods
Figs. S1 to S3
Tables S1 and S2
Movies S1 to S3
24 January 2017; accepted 1 August 2017
Paneth cells secrete lysozyme via
secretory autophagy during bacterial
infection of the intestine
Shai Bel,1 Mihir Pendse,1 Yuhao Wang,1 Yun Li,1 Kelly A. Ruhn,1 Brian Hassell,1
Tess Leal,1 Sebastian E. Winter,2 Ramnik J. Xavier,3,4,5 Lora V. Hooper1,6*
Intestinal Paneth cells limit bacterial invasion by secreting antimicrobial proteins, including
lysozyme. However, invasive pathogens can disrupt the Golgi apparatus, interfering with
secretion and compromising intestinal antimicrobial defense. Here we show that during
bacterial infection, lysozyme is rerouted via secretory autophagy, an autophagy-based
alternative secretion pathway. Secretory autophagy was triggered in Paneth cells by
bacteria-induced endoplasmic reticulum (ER) stress, required extrinsic signals from innate
lymphoid cells, and limited bacterial dissemination. Secretory autophagy was disrupted
in Paneth cells of mice harboring a mutation in autophagy gene Atg16L1 that confers
increased risk for Crohn’s disease in humans. Our findings identify a role for secretory
autophagy in intestinal defense and suggest why Crohn’s disease is associated with
genetic mutations that affect both the ER stress response and autophagy.
The mammalian intestine is home to a diverse population of bacteria, which includes patho- gens that can disrupt host cellular functions. The intestinal epithelium defends against bacterial encroachment through multiple
mechanisms, including antimicrobial protein
secretion and destruction of invading bacteria
through autophagy (1). Paneth cells are special-
ized intestinal epithelial cells that secrete abun-
dant antimicrobial proteins, including lysozyme;
thus, disrupting Paneth cell secretion can lead to
inflammatory disease (2–4). Pathogenic microbes
can trigger endoplasmic reticulum (ER) stress
that interferes with protein secretion (5, 6) and
compromises antimicrobial protein delivery, rais-
ing the question of how Paneth cells preserve
their antimicrobial function during pathogen-
SCIENCE sciencemag.org 8 SEPTEMBER 2017 • VOL 357 ISSUE 6355 1047
1Department of Immunology, The University of Texas
Southwestern Medical Center, Dallas, TX 75390, USA.
2Department of Microbiology, The University of Texas
Southwestern Medical Center, Dallas, TX 75390, USA.
3Broad Institute, Cambridge, MA 02142, USA. 4Center for
Computational and Integrative Biology, Massachusetts
General Hospital, Boston, MA 02114, USA. 5Gastrointestinal
Unit and Center for the Study of Inflammatory Bowel
Disease, Massachusetts General Hospital, Harvard Medical
School, Boston, MA 02142, USA. 6The Howard Hughes
Medical Institute, The University of Texas Southwestern
Medical Center, Dallas, TX 75390, USA.
*Corresponding author. Email: firstname.lastname@example.org
RESEARCH | REPORTS