**Meet the editor**

After obtaining his MD at the Universitat Autònoma de Barcelona, Pere-Joan Cardona started an internship in Clinical Microbiology in 1994, in the Hospital Germans Trias i Pujol, where he was familiarized with the problem of TB in its clinical and diagnostic challenges. Invited by Ian Orme at CSU, he was trained on the development of TB experimental models. PhD was obtained in 1999. He

became Head of the Experimental Tuberculosis Unit at the Institut Germans Trias i Pujol of Badalona and Assistant Professor of Microbiology at UAB. He has been involved for the last 15 years in the study of the pathophysiology of TB infection. Additionally, he has authored 70 peer-reviewed publications in the field and is responsible for the development of different experimental models in mice, guinea pigs, goats and mini-pigs, and in the development of new drug regimens and vaccines against TB.

Contents

**Preface IX** 

Chapter 1 **Ten Questions to Challenge the** 

Pere-Joan Cardona

Irina Lyadova

**Part 1 Dissecting the Interphase Host-Pathogen 1** 

**Natural History of Tuberculosis 3** 

Chapter 3 **Host–Pathogen Interactions in Tuberculosis 43** 

**of** *Mycobacterium tuberculosis* **Cell Envelope Components During Infection:** 

Clara Espitia, Eden Rodríguez, Lucero Ramón-Luing, Gabriela Echeverría-Valencia and Antonio J. Vallecillo

Chapter 2 **Inflammation and Immunopathogenesis of Tuberculosis Progression 19** 

Chapter 4 **Broadening Our View About the Role** 

**A Battle for Survival 77** 

**and a Koch's Bacillus Funeral:** 

**Actin, Lipids, Phagosome Maturation and Inflammasome Activation 123** 

**in Mycobacterial Infections 149** 

Chapter 7 **Epithelioid Cell: A New Opinion on Its Nature,** 

**Parentage, Histogenesis, Cytomorphogenesis, Morphofunctional Potency, Role in Pathogenesis and Morphogenesis of Tuberculous Process 179** 

B.E. Garcia-Perez, N.S. Castrejon-Jimenez and J. Luna-Herrera

Jordi B. Torrelles

Chapter 5 **For Host Factors Weddings** 

Chapter 6 **The Role of Non-Phagocytic Cells** 

Sergey Arkhipov

Elsa Anes

### Contents

#### **Preface** XIII


X Contents


Contents VII

Chapter 18 **Towards a New Challenge in TB Control:** 

Armando Acosta, Yamile Lopez,

Chapter 19 **Identification of CD8+ T Cell Epitopes**

Chapter 20 **The Hidden History of Tuberculin 445** 

**with IgA and Cytokines 457**  Rajko Reljic and Juraj Ivanyi

Chapter 21 **Immunotherapy of Tuberculosis**

Chapter 22 **Therapy for Tuberculosis:** *M. vaccae*

Chapter 23 **Adjuvant Interferon Gamma in** 

and Isis Cayón-Escobar

**Development of Antibody-Based Protection 415**

Norazmi Mohd Nor, Rogelio Hernández Pando, Nadine Alvarez and Maria Elena Sarmiento

**Against** *Mycobacterium tuberculosis* **433**  Fei Chen, Yanfeng Gao and Yuanming Qi

Cristina Vilaplana and Pere-Joan Cardona

**Inclusion into Routine Treatment 473** 

Idrian García-García, María T Milanés-Virelles, Pedro A López-Saura, Roberto Suárez-Méndez, Magalys Valdés-Quintana, Norma Fernández-Olivera, Carmen M Valenzuela-Silva, Lidia González- Méndez, Yamilet Santos-Herrera, Gladys Abreu-Suárez

Chapter 24 **Biochemical and Immunological Characterization** 

Chapter 25 **P27-PPE36 (Rv2108)** *Mycobacterium tuberculosis*

Vincent Le Moigne and Wahib Mahana

Diana G. Dlugovitzky, Cynthia Stanford and John Stanford

**the Management of Multidrug - Resistant Tuberculosis 501**

**of the** *Mycobacterium tuberculosis* **28 kD Protein 525** 

**Surface Localization and Immunological Activities 539**

Elinos-Báez Carmen Martha and Ramírez González

**Antigen – Member of PPE Protein Family with** 

Chapter 9 **Role of TNF in Host Resistance to Tuberculosis Infection: Membrane TNF Is Sufficient to Control Acute Infection 235**  Valerie Quesniaux, Irene Garcia, Muazzam Jacobs and Bernhard Ryffel

Chapter 10 **Immunoregulatory Role of GM-CSF in Pulmonary Tuberculosis 253**  Zissis C. Chroneos and Chinnaswamy Jagannath

Chapter 11 **Double Edge Sword: The Role of Neutrophils in Tuberculosis 277**  Patricia González-Cano, Rommel Chacón-Salinas, Victoria Ramos-Kichik, Rogelio Hernández-Pando, Jeanet Serafín-López, Georgina Filio-Rodríguez, Sergio Estrada-Parra and Iris Estrada-García


#### **Part 2 Manipulating the Immune Responses to Favor the Host 367**




VI Contents

Chapter 8 **How** *Mycobacterium tuberculosis* **Manipulates Innate** 

Chapter 9 **Role of TNF in Host Resistance to Tuberculosis Infection:** 

Zissis C. Chroneos and Chinnaswamy Jagannath

**The Role of Neutrophils in Tuberculosis 277** Patricia González-Cano, Rommel Chacón-Salinas, Victoria Ramos-Kichik, Rogelio Hernández-Pando, Jeanet Serafín-López, Georgina Filio-Rodríguez, Sergio Estrada-Parra and Iris Estrada-García

**as Innate Promoters of Local Type 1 Immunity** 

Chapter 14 **MHC Polymorphism and Tuberculosis Disease 343** 

**Identification of New SNPs and Association with Tuberculosis Outcome in Brazilians 357** L.B. Spinassé, M.Q.P. Lopes, A.B. Miranda, R.L.F. Teixeira, F.C.Q. Mello, J.R. Lapa e Silva, P.N. Suffys and A.R. Santos

Chapter 15 **Partial Mapping of the IL-10 Promoter Region:** 

Chapter 16 **Vaccines Against** *Mycobacterium tuberculosis***: An Overview from Preclinical Animal** 

**Studies to the Clinic 369** 

Toshi Nagata and Yukio Koide

Chapter 17 **Immune Responses Against**

Pablo Schierloh, Silvia De La Barrera and Maria Sasiain

**with Potential Application on Differential Diagnosis 297** 

Khalid Sadki, Youssef Bakri, M'Hamed Tijane and Saaid Amzazi

**Part 2 Manipulating the Immune Responses to Favor the Host 367** 

Rhea N. Coler, Susan L. Baldwin, and Steven G. Reed

*Mycobacterium tuberculosis* **and the Vaccine Strategies 391**

Susanna Brighenti and Maria Lerm

Valerie Quesniaux, Irene Garcia, Muazzam Jacobs and Bernhard Ryffel

**in Pulmonary Tuberculosis 253**

Chapter 12 **Role of NK Cells in Tuberculous Pleurisy** 

Chapter 13 **Are Polyfunctional Cells Protective in**  *M. tuberculosis* **Infection? 313** Nadia Caccamo and Francesco Dieli

Chapter 10 **Immunoregulatory Role of GM-CSF** 

Chapter 11 **Double Edge Sword:** 

**and Adaptive Immunity – New Views of an Old Topic 207**

**Membrane TNF Is Sufficient to Control Acute Infection 235**


Preface

*Mycobacterium tuberculosis* and the *Homo sapiens*.

The most intriguing property of *Mycobacterium tuberculosis* is its ability to remain for years in the host tissue, in a discrete and non-replicative way, reactivating and causing disease. This skill has stimulated multiple studies to try to discern why the host is not able to effectively eradicate it, instead of "tolerating" its persistence in the tissues. In this book, different specialists dissect the different factors and cells implied in the natural and adaptive immune response against *Mycobacterium tuberculosis* in an attempt to understand the extent to which the bacilli has adapted itself to the host and to its final target. On the other hand, there is a section in which other specialists discuss how to manipulate this immune response to obtain innovative prophylactic and therapeutic approaches to truncate the intimal co-evolution between

**Dr. Pere-Joan Cardona** 

Catalunya, Spain

Institut Germans Trias i Pujol (IGTP)

### Preface

The most intriguing property of *Mycobacterium tuberculosis* is its ability to remain for years in the host tissue, in a discrete and non-replicative way, reactivating and causing disease. This skill has stimulated multiple studies to try to discern why the host is not able to effectively eradicate it, instead of "tolerating" its persistence in the tissues. In this book, different specialists dissect the different factors and cells implied in the natural and adaptive immune response against *Mycobacterium tuberculosis* in an attempt to understand the extent to which the bacilli has adapted itself to the host and to its final target. On the other hand, there is a section in which other specialists discuss how to manipulate this immune response to obtain innovative prophylactic and therapeutic approaches to truncate the intimal co-evolution between *Mycobacterium tuberculosis* and the *Homo sapiens*.

> **Dr. Pere-Joan Cardona**  Institut Germans Trias i Pujol (IGTP) Catalunya, Spain

**Part 1** 

**Dissecting the Interphase Host-Pathogen** 
