Stephanie Constant / MITMAssistant Professor

Dept. of Microbiology, Immunology and Tropical Medicinemtmslc@gwumc.edu

994-1138

Hookworm E/S products and host immune evasion and

Cyclophilin-CD147 interactions in inflammation

Stephanie Constant / MITM

Na Ac

80

4555

30

21

14

66

97116200

Hsieh et al. 2004 J. Immunol. 173:2699Loukas et al. 2005 FEMS 43:115

Funding: R01 AI-059280-01

PROJECT 1

Hookworm E/S products and host immune evasion

PROJECT 1

Hookworm E/S products and host immune evasion

IFN-

(p

g/m

l)

0

500

1,000

1,500

+IL2+IL12

+ES +IL2+IL12+ES

ES products augment IFN- production by >30 fold in

human NK cells

Stephanie Constant / MITM

Egg-negative

(USA)

Egg-positive(Brazil)

0

25

50

75

Patient Category%

bio

ES+ N

K ce

lls

Egg-negative(Brazil)

Patients with activehookworm infection donot bind ES products

ES binding

ES products bind onlyto NK cells

Stephanie Constant / MITM

Arora et al. 2005 J. Immunol. 175:517Yurchenko et al. 2005 Immunology 117:301

Funding: R01 AI-067254-01

PROJECT 2

Cyclophilin-CD147 interactions in inflammation

0 50 100 500 FMLP0

1

2

3

4

5

6

7

CyPA (ng/ml)

Che

mot

actic

inde

x

Medium CyPA CyPA+CD147

CyPA+isotype

0

1

2

3

4

5

***

Che

mot

actic

inde

x

Extracellular cyclophilins induceleukocyte chemotaxis

Cyclophilin-mediated chemotaxis is dependent on CD147 signaling

Stephanie Constant / MITMPROJECT 2

Cyclophilin-CD147 interactions in inflammation

10

0123456789

21 23 27 30 34 37 41 44 48 51 55 58

Clin

ical

sco

re

isotype

anti-CD147

** *

*

Mouse model of rheumatoid arthritis

Days

0

0.5

1.0

1.5

2.0

2.5

3.125 6.25 12.5 25 50

Methacholine (mg/ml)

Rat

io P

enh

baselineanti-CD147isotype control

****

Mouse model ofallergic asthma

Gwinn et al. 2006 J. Immunol. 177:4870