Cryptococcus Flashcards

1
Q

How do you get?

A

Breath in spores or yeast from bird shit or tree

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2
Q

What is the biggest risk of cryptococcus?

A

cryptococcal meningitis

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3
Q

Which morphology is dangerous?

A

yeast

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4
Q

What is special about the yeast form?

A

thick capsule

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5
Q

What does the capsule do?

A
  • hides PAMPs
  • reduces macrophage attachment
  • reduces phagocytosis
  • produces soluble GXM which UP IL10 (antiinflam)
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6
Q

How did they prove the capsule hides PAMPs?

A
  • CAP + PRR = little recognition
  • CAP- + PRR = recognition and phagocytosis
  • CAP- + beta glucan PRR competitor + PRR = little recognition
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7
Q

What do soluble GXM do?

A
  • UP IL10 (antiinflammatory)
  • DOWN TNFalpha
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8
Q

How is melanin created?

A

Laccase uses L-DOPA or epinephrine from host

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9
Q

What is melanin important for?

A

CNS infection

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10
Q

What do melanin do?

A

inhibits ROS (esp. H2O2)

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11
Q

What does APP1 stand for?

A

AntiPhagocytic Protein 1

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12
Q

What do APP1 do?

A

prevents complement mediated phagocytosis

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13
Q

What’s the brain fungal burden for healthy host and APP1- and why?

A
  • DOWN because need phagocytosis to get into brain
  • healthy host has Th1 to activate macrophages and kill crypto passengers
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14
Q

What’s the brain fungal burden for HIV+ host and APP1- and why?

A
  • UP because more phagocytosis and no Th1 to activate macrophages
  • crypto gets ubered to the brain
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15
Q

What do vomocytosis do?

A

induces macrophage to puke up only crypto

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16
Q

What causes vomocytosis?

A

encapsulated alive crypto actively induces it

17
Q

What do Titan cells do?

A

be too big to phagocytose

18
Q

Are antibodies sufficient and or required?

A

they do nothing

19
Q

Are Th1 cells sufficient and or required?

20
Q

What do Th2 response do?

A
  • UP IL4 (Th0 to Th2)
  • UP B cell and antibody production
  • DOWN IL12 and IFNgamma (proinflam)
  • Hurts survival
21
Q

IL12 and cryptococcus

A
  • shifts Th population towards protective Th1
  • reduces fungal burden if you give early enough
22
Q

Dendritic cells and cryptococcus

A
  • push Th population towards Th2 which is NOT protective
23
Q

chitin vs Th2 and why

A
  • DOWN chitin = DOWN Th2
  • DOWN APing from dendritic cells
24
Q

What do chit1 and AMCase do?

A

break down chitin into C7 bits which dendritic cells can AP

25
Why is cryptococcus gatii extra bad?
UP Intracellular Proliferation Rate (IPR) = larger mitochondria = more virulent
26
How did cryptococcus evolve?
* survive soil predators (acanthamoeba and nematodes)
27
How do you discover a novel virulence factor?
1000s of mutant yeast + WT host
28
How do you discover host defenses?
WT strains or attenuated mutants + 1000s of mutant worms
29
How do you discover interacting host-pathogen pathways?
1000s of mutant yeast + 1000s of mutant worms
30
Risk factors for cryptococcus, esp. CNS
HIV+
31
What are the 6 virulence factors of cryptococcus?
* capsule - hide PAMPs * GXM - supress immune * melanin - ROS and RNS * APP1 - block complement phagocytosis * vomocytosis - reverse phagocytosis * Titan cells - be too big to eat
32
What are the cryptococcus PAMPs and PRRs?
* mannan - MR * beta glucan - Dectin1