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371) Interestingly, overexpressing galectin-8 helps macrophages target and control Mtb, highlighting the importance of galectin-8 in the innate immune response to Mtb.
* Galectin-8 Senses Phagosomal Damage and Recruits Selective Autophagy Adapter TAX1BP1 To Control Mycobacterium tuberculosis Infection in Macrophages.
- Mycobacterium tuberculosis (Mtb) causes one of the deadliest infectious diseases worldwide. Upon infection, Mtb is phagocytosed by macrophages and uses its virulence-associated ESX-1 secretion system to modulate the host cell. We showed previously that the ESX-1 secretion system perturbs the Mtb-containing phagosome, and a population (∼30%) of intracellular Mtb is tagged with ubiquitin and targeted to selective autophagy. However, our understanding of how macrophages sense and respond to damaged Mtb-containing phagosomes remains incomplete. Here, we demonstrate that several cytosolic glycan-binding proteins called galectins recognize Mtb-containing phagosomes; in macrophage cell lines and in primary macrophages, galectin-3, -8, and -9 are all recruited to the same Mtb population that colocalizes with selective autophagy markers (ubiquitin, p62, and LC3). To test whether galectins are required for controlling Mtb replication in macrophages, we generated CRISPR/Cas9 knockouts and found that galectin-8-/- and galectin-3/8/9-/- macrophages were similarly defective in targeting Mtb to selective autophagy and controlling replication. This suggests galectin-8 plays a unique role in anti-Mtb autophagy. In investigating galectin-8's role, we identified a novel and specific interaction between galectin-8 and the selective autophagy adapter TAX1BP1 and found that this galectin-8/TAX1BP1 interaction was necessary for macrophages to efficiently target Mtb to selective autophagy. Remarkably, overexpressing galectin-8 increased targeting of Mtb to autophagy and limited Mtb replication. Taken together, these data demonstrate that while several galectins are capable of recognizing damaged Mtb-containing phagosomes, galectin-8 plays a privileged role in recruiting downstream autophagy machinery and may represent a promising target for host-directed tuberculosis therapies. IMPORTANCE Mycobacterium tuberculosis (Mtb) infects one-quarter of the global population and causes one of the deadliest infectious diseases worldwide. Macrophages are the first line of defense against Mtb infection and are typically incredibly efficient at destroying intracellular pathogens, but Mtb has evolved to survive and replicate in this harsh environment. Previous work has found that a portion of intracellular Mtb bacilli damage their phagosomes, leaving them vulnerable to detection by the host and delivery to an antibacterial pathway called selective autophagy. Here, we show that in macrophages, galectin-8 recognizes damaged Mtb-containing phagosomes and targets Mtb to selective autophagy; we found that galectin-8, unlike other highly similar and closely related galectins, is required for targeting and controlling Mtb in macrophages. The specific role for galectin-8 appears to stem from its interaction with TAX1BP1, a selective autophagy adapter protein. Interestingly, overexpressing galectin-8 helps macrophages target and control Mtb, highlighting the importance of galectin-8 in the innate immune response to Mtb.
=>1.管理する, 制御する, 統制する, 抑える, 2.コントロール, 実験対象, 管理, 対照標準
Overview of noun control
The noun control has 11 senses (first 9 from tagged texts)
1. (19) control -- (power to direct or determine; "under control")
2. (16) control -- (a relation of constraint of one entity (thing or person or group) by another;
"measures for the control of disease"; "they instituted controls over drinking on campus")
3. (7) control -- ((physiology) regulation or maintenance of a function or action or reflex etc;
"the timing and control of his movements were unimpaired"; "he had lost control of his sphincters")
4. (5) control condition, control -- (a standard against which other conditions can be compared in a
scientific experiment; "the control condition was inappropriate for the conclusions he wished to
draw")
5. (5) control -- (the activity of managing or exerting control over something; "the control of the
mob by the police was admirable")
6. (4) dominance, ascendance, ascendence, ascendancy, ascendency, control -- (the state that exists
when one person or group has power over another; "her apparent dominance of her husband was really
her attempt to make him pay attention to her")
7. (3) restraint, control -- (discipline in personal and social activities; "he was a model of
polite restraint"; "she never lost control of herself")
8. (2) command, control, mastery -- (great skillfulness and knowledge of some subject or activity;
"a good command of French")
9. (1) control, controller -- (a mechanism that controls the operation of a machine; "the speed
controller on his turntable was not working properly"; "I turned the controls over to her")
10. control -- (a spiritual agency that is assumed to assist the medium during a seance)
11. control -- (the economic policy of controlling or limiting or curbing prices or wages etc.;
"they wanted to repeal all the legislation that imposed economic controls")
Overview of verb control
The verb control has 8 senses (first 4 from tagged texts)
1. (28) control, command -- (exercise authoritative control or power over; "control the budget";
"Command the military forces")
2. (20) control, hold in, hold, contain, check, curb, moderate -- (lessen the intensity of; temper;
hold in restraint; hold or keep within limits; "moderate your alcohol intake"; "hold your tongue";
"hold your temper"; "control your anger")
3. (7) operate, control -- (handle and cause to function; "do not operate machinery after imbibing
alcohol"; "control the lever")
4. (1) manipulate, keep in line, control -- (control (others or oneself) or influence skillfully,
usually to one's advantage; "She manipulates her boss"; "She is a very controlling mother and
doesn't let her children grow up"; "The teacher knew how to keep the class in line"; "she keeps in
line")
5. control, verify -- (check or regulate (a scientific experiment) by conducting a parallel
experiment or comparing with another standard; "Are you controlling for the temperature?")
6. control -- (verify by using a duplicate register for comparison; "control an account")
7. see, check, insure, see to it, ensure, control, ascertain, assure -- (be careful or certain to do
something; make certain of something; "He verified that the valves were closed"; "See that the
curtains are closed"; "control the quality of the product")
8. master, control -- (have a firm understanding or knowledge of; be on top of; "Do you control
these data?")
--- WordNet end ---