Cryptococcus

Question 1

How do you get?

Answer 1

Breath in spores or yeast from bird shit or tree

Question 2

What is the biggest risk of cryptococcus?

Answer 2

cryptococcal meningitis

Question 3

Which morphology is dangerous?

Answer 3

yeast

Question 4

What is special about the yeast form?

Answer 4

thick capsule

Question 5

What does the capsule do?

Answer 5

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

Question 6

How did they prove the capsule hides PAMPs?

Answer 6

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

Question 7

What do soluble GXM do?

Answer 7

• UP IL10 (antiinflammatory)
• DOWN TNFalpha

Question 8

How is melanin created?

Answer 8

Laccase uses L-DOPA or epinephrine from host

Question 9

What is melanin important for?

Answer 9

CNS infection

Question 10

What do melanin do?

Answer 10

inhibits ROS (esp. H2O2)

Question 11

What does APP1 stand for?

Answer 11

AntiPhagocytic Protein 1

Question 12

What do APP1 do?

Answer 12

prevents complement mediated phagocytosis

Question 13

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

Answer 13

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

Question 14

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

Answer 14

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

Question 15

What do vomocytosis do?

Answer 15

induces macrophage to puke up only crypto

Question 16

What causes vomocytosis?

Answer 16

encapsulated alive crypto actively induces it

Question 17

What do Titan cells do?

Answer 17

be too big to phagocytose

Question 18

Are antibodies sufficient and or required?

Answer 18

they do nothing

Question 19

Are Th1 cells sufficient and or required?

Answer 19

yes

Question 20

What do Th2 response do?

Answer 20

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

Question 21

IL12 and cryptococcus

Answer 21

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

Question 22

Dendritic cells and cryptococcus

Answer 22

• push Th population towards Th2 which is NOT protective

Question 23

chitin vs Th2 and why

Answer 23

• DOWN chitin = DOWN Th2
• DOWN APing from dendritic cells

Question 24

What do chit1 and AMCase do?

Answer 24

break down chitin into C7 bits which dendritic cells can AP

Question 25

Why is cryptococcus gatii extra bad?

Answer 25

UP Intracellular Proliferation Rate (IPR) = larger mitochondria = more virulent

Question 26

How did cryptococcus evolve?

Answer 26

• survive soil predators (acanthamoeba and nematodes)

Question 27

How do you discover a novel virulence factor?

Answer 27

1000s of mutant yeast + WT host

Question 28

How do you discover host defenses?

Answer 28

WT strains or attenuated mutants + 1000s of mutant worms

Question 29

How do you discover interacting host-pathogen pathways?

Answer 29

1000s of mutant yeast + 1000s of mutant worms

Question 30

Risk factors for cryptococcus, esp. CNS

Answer 30

HIV+

Question 31

What are the 6 virulence factors of cryptococcus?

Answer 31

• capsule - hide PAMPs
• GXM - supress immune
• melanin - ROS and RNS
• APP1 - block complement phagocytosis
• vomocytosis - reverse phagocytosis
• Titan cells - be too big to eat

Question 32

What are the cryptococcus PAMPs and PRRs?

Answer 32

• mannan - MR
• beta glucan - Dectin1