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Articles 1 - 30 of 58
Full-Text Articles in Medicine and Health Sciences
The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta
The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta
All ETDs from UAB
Several studies have established the importance of epigenetic regulation of gene transcription in the brain during memory consolidation. Epigenetic mechanisms involve modifying the DNA or the associated histone proteins to determine the transcriptional outcome of a gene. The work encompassed in this dissertation serves as an initial investigation for the role of histone lysine methylation mechanisms in regulating gene activation and suppression in the medial temporal lobe that includes entorhinal cortex (EC), hippocampus, and amygdala during memory consolidation. To this end, we found that di-methylation of histone H3 at lysine 9 (H3K9me2) which promotes gene suppression was specific to associative …
Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon
Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon
All ETDs from UAB
Type I diabetes (T1D) is an autoimmune disease in which ß cells are destroyed by the immune system; however, role of infections in type I diabetes (T1D) pathogenesis is unclear. Reports suggesting that childhood Group A Streptococcal (GAS) infections protected against T1D prompted us to study how antibodies to N-acetyl-D-glucosamine (GlcNAc), which are induced by GAS infection, influenced T1D development. We found that GlcNAc-specific antibodies reacted with ß cell secretory granules, and neonatal NOD mice immunized with GAS or given GAS-immune sera were protected from spontaneous diabetes. Monoclonal GlcNAc-specific IgM blocked activation and effector responses to islet antigens by diabetogenic …
Suppression Of A Nonsense Mutation In A Mouse Model Of Hurler Syndrome, Dan Wang
Suppression Of A Nonsense Mutation In A Mouse Model Of Hurler Syndrome, Dan Wang
All ETDs from UAB
Nonsense suppression therapy utilizes compounds that suppress translation termination at disease-causing premature termination codons (PTCs) to restore full-length, functional protein synthesis. This approach may provide a treatment for many diseases caused by nonsense mutations including Hurler syndrome (mucopolysaccharidosis type I - Hurler, MPS I-H). MPS I-H is a lysosomal storage disease caused by severe &alpha-L-iduronidase deficiency and subsequent lysosomal glycosaminoglycan (GAG) accumulation. In this work, we investigated the effectiveness of nonsense suppression therapy as a treatment for MPS I-H. We first generated a targeted knock-in mouse model that carries the Idua-W392X nonsense mutation homologous to the human IDUA-W402X mutation frequently …
Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells
Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells
All ETDs from UAB
Mycobacterium tuberculosis is a dangerous human pathogen that has the capacity to adapt to and survive within the harsh phagosomal environment of macrophages. One obstacle that must be overcome by pathogens is to acquire iron, an essential component and cofactor of proteins required for vital cellular processes. M. tuberculosis meets its iron demands in the face of an array of sequestration strategies of the host by synthesizing and secreting two siderophores called mycobactin and carboxymycobactin. Siderophores are low molecular weight high affinity iron binding compounds that steal iron away from host stores and have been shown to be important for …
Effects Of Stress On Growth Hormone Receptor Signaling, Ryan Marshall Corrick
Effects Of Stress On Growth Hormone Receptor Signaling, Ryan Marshall Corrick
All ETDs from UAB
Growth hormone (GH) regulates body composition via stimulation of protein synthesis and catabolism of adipose tissue, generally promoting maintenance of lean body mass. Following severe injury, GH resistance contributes to muscle protein wasting, adversely impacting morbidity and mortality. In this dissertation research, we sought to determine the mechanisms of GH resistance following injury. To accomplish this, we evaluated GH signaling in a mouse model of severe injury. In the first section of this thesis, we demonstrate severe impairments in hepatic GH signaling occurring in association with an apparent, hemorrhage-dependent cleavage of the GH receptor (GHR). In the second section, we …
Hcn Channels And Regulation Of Neocortical Network Activity, Asher Albertson
Hcn Channels And Regulation Of Neocortical Network Activity, Asher Albertson
All ETDs from UAB
Hyperpolarization activated non-specifc cation (HCN) channels are unique channels that activate following membrane hyperpolarization. Expressed primarily along the apical dendrites of pyramidal neurons, they pass a non-inactivating, inward current (Ih). HCN channel activation at resting membrane potentials profoundly impacts the synaptic and intrinsic properties of pyramidal neurons. Activated channels decrease intrinsic membrane excitability, hyperpolarize the resting membrane potential, and increase excitatory post-synaptic potentials (EPSP) summation. Loss of HCN channels is commonly observed in models of epilepsy. This dissertation tests the hypothesis that the influence of HCN channels on individual neuron excitability translates to an influence on network excitability. Furthermore, we …
Characterizing The Transcriptional Complexity Of Pkhd1/Pkhd1, Ravindra Boddu
Characterizing The Transcriptional Complexity Of Pkhd1/Pkhd1, Ravindra Boddu
All ETDs from UAB
Mutations in PKHD1 gene cause autosomal recessive polycystic kidney disease. Our previous studies have shown that human PKHD1 and its mouse orthologue, Pkhd1, undergo an extensive pattern of alternative splicing. Pkhd1 is primarily expressed in renal and biliary tubular structures. Translation products of these alternative spliced transcripts are predicted to generate isoforms expressed in plasma membrane, primary cilium and cytoplasm. We have characterized the cyli mouse model of ARPKD and identified a frameshift mutation, c.7589delGGinsT, in Pkhd1 exon 48. In this thesis we have characterized the mouse Pkhd1cyli/cyli model (liver restricted phenotype) and evaluated the transcriptome in terms of alternative …
Regulation Of Clc-3 In Human Malignant Glioma, Vishnu Anand Cuddapah
Regulation Of Clc-3 In Human Malignant Glioma, Vishnu Anand Cuddapah
All ETDs from UAB
Malignant gliomas are the most common and deadly form of primary brain cancer afflicting adults. Current treatment regimens, including surgical debulking, radiotherapy, and chemotherapy, have limited efficacy, and median patient survival remains only 14 months. Therefore, novel therapies must target different aspects of glioma biology. Two of the most striking features of this cancer are the unusual ability of glioma cells to robustly proliferate and migrate in the brain, and recent evidence suggests that ClC-3, a voltage-gated Cl- channel/transporter is implicated in both of these processes. We hypothesize that ClC-3 may facilitate proliferation and migration by promoting hydrodynamic shape and …
Structural And Molecular Studies Of Nucleic Acid Chaperones, Lei Ding
Structural And Molecular Studies Of Nucleic Acid Chaperones, Lei Ding
All ETDs from UAB
Nucleic acids are the storage of genetic information that needs to be expressed and inherited. As abundant cellular macromolecules they are also major players of a wide variety of biological processes. They usually undergo post-transcriptional modifications and/or fold into higher order structures in order to accomplish their distinct functions. Most biological events involving nucleic acids are achieved by proteins that interact with them. The functionality requires specific recognition of nucleic acids by proteins at molecular level. Nucleic acid chaperones are a group of nucleic acids binding proteins that associate with structured RNAs or DNAs and assist correct folding of their …
Scaffold-Mediated Size Determination Of Bacteriophage Capsids By Mobile Genetic Elements, Altaira Davida Dearborn
Scaffold-Mediated Size Determination Of Bacteriophage Capsids By Mobile Genetic Elements, Altaira Davida Dearborn
All ETDs from UAB
Bacteriophage can mediate the transfer of unrelated mobile genetic elements (MGE) from a carrier bacterial cell to the susceptible population around it. This transfer results in the spread of virulence or other accessory genes encoded on the MGE. During viral particle assembly, the MGE can discourage the formation of viable bacteriophage progeny by limiting the size of the particles to those large enough to encapsidate the MGE, but too small to fit the complete bacteriophage genome which is three times larger. Here, I present models for size determination by an external scaffolding protein which is independent of and dominant over …
Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman
Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman
All ETDs from UAB
Hepatocellular carcinoma (HCC) incidence in the US is dramatically increasing. Five-year survival has remained 3-5% for the past several decades, demonstrating urgent need for additional therapies. Intrabuccal administration of amplitude-modulated radiofrequency electromagnetic fields (RF EMF) is a novel, minimally invasive treatment modality. Clinical evidence demonstrates this treatment approach elicits therapeutic responses in cancer patients. In vitro we have described a phenotype in HCC cells following RF EMF exposure that included proliferative inhibition, modulation of gene expression, and disruption of the mitotic spindle. This phenotype was specific for HCC cells exposed to HCC-specific RF EMF. We have demonstrated similar efficacy in …
Regulatory T Cells In The Fvb.Mdr1a-/- Model Of Colitis, Scott Tanner
Regulatory T Cells In The Fvb.Mdr1a-/- Model Of Colitis, Scott Tanner
All ETDs from UAB
Regulatory T cells (Treg) are necessary for the maintenance of immune homeostasis, and have been implicated in several autoimmune diseases, including inflammatory bowel disease (IBD). Most murine studies focusing on the function of Tregs have been done on the C57BL/6 or BALB/c background, creating a bias towards these two strains. In addition, it has been shown that C57BL/6 and BALB/c Tregs function in different manners. To further investigate potential strain differences in Treg phenotype and function, we chose to analyze FVB/N Tregs. Several differences were observed, including de-creased FVB/N Treg suppression in a non-cell contact dependent manner, decreased FVB/N and …
Modulation Of Capsule Production In Serotype 3 Streptococcus Pneumoniae, Melissa Ellis
Modulation Of Capsule Production In Serotype 3 Streptococcus Pneumoniae, Melissa Ellis
All ETDs from UAB
Streptococcus pneumoniae is a Gram-positive pathogen and an important cause of community-acquired pneumonia and meningitis, and it can also cause otitis media and bacteremia. A major virulence factor of S. pneumoniae is its polysaccharide capsule which functions to prevent complement-mediated opsonophagocytosis. At least 93 distinct serotypes that vary in sugar composition and structure exist. S. pneumoniae can asymptomatically colonize the nasopharynx and transition to other body sites such as the lungs and blood causing invasive disease. The ability to regulate capsule production in these vastly different environments is critical for survival as low levels of capsule are necessary for colonization, …
Functional Collaboration Between Igf-1 Receptor And Growth Hormone Signaling Pathway, Yujun Gan
Functional Collaboration Between Igf-1 Receptor And Growth Hormone Signaling Pathway, Yujun Gan
All ETDs from UAB
GH receptor (GHR) binds GH in its extracellular domain (ECD) to activate the GHR-associated cytoplasmic tyrosine kinase, JAK2. IGF-1 binds IGF-1R, a disulfide-linked heterotetramer with tyrosine kinase activity in its intracellular domain (ICD). Classically, IGF-1 is a GH effector in a “linear” GH→GHR→IGF-1→IGF-1R pathway. Our recent studies suggest IGF-1R also subserves GH signaling in several novel ways: 1) GH induces a GHR-JAK2-IGF-1R complex, whose formation is independent of tyrosine phosphorylation of any of the partners; 2) Cotreatment with IGF-1 augments acute GH signaling; 3) deletion of IGF-1R in primary osteoblasts or human prostate cancer cells blunts acute GH signaling. In …
Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh
Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh
All ETDs from UAB
Apoptosis in metazoan organisms plays critical roles in normal development, tissue homeostasis and immunity, and its disturbed regulation leads to many pathological states, including cancer, autoimmunity, infection and degenerative disorders. Apoptosis can be triggered by the engagement of `death receptors' of the tumor necrosis factor receptor family on the cell surface or by diverse intracellular signals that act upon the BCL2 (B-cell CLL/lymphoma 2) protein family, which controls the integrity of the mitochondrial outer membrane through the complex interactions of family members. Both the pathways lead to cellular demolition by dedicated proteases termed caspases. Different BH3-only proteins (or combinations of …
Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps
Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps
All ETDs from UAB
Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein …
Discovery And Characterization Of Streptococcus Pneumoniae Serotype 11e Reveals A Novel Model Of Serotype Evolution, Juan Jose Calix
Discovery And Characterization Of Streptococcus Pneumoniae Serotype 11e Reveals A Novel Model Of Serotype Evolution, Juan Jose Calix
All ETDs from UAB
The facultative pathogen Streptococcus pneumoniae is capable of producing a polysaccharide (PS) capsule that prevents bacterial recognition and clearance by the host immune system. Over 90 antigenically distinct capsule serotypes have been identified. Because anti-capsule antibodies can mediate bacterial clearance, capsule diversity is critical to S. pneumoniae survival. However, the mechanisms of capsule evolution remain unclear. Due to the complex interaction of capsule synthesis (cps) genes, it is commonly thought that pneumococcal serotypes evolve once and that all clinically relevant serotypes are genetically derived from a single founding clone. In this dissertation we demonstrate a novel mechanism of capsule evolution …
Cytokine Signaling In A Mouse Model Of Parkinson's Disease, Shuwen Cao
Cytokine Signaling In A Mouse Model Of Parkinson's Disease, Shuwen Cao
All ETDs from UAB
The protein alpha-synuclein (α-SYN), which is found in the Lewy bodies of dopaminergic (DA) neurons in the substantia nigra (SN), has an important role in the pathogenesis of Parkinson's disease (PD). Fcγ receptors (FcγR) are proteins present on the surface of microglia, which bind immunoglobulin G (IgG) and other ligands. Our studies in an AAV-synuclein mouse model of PD showed that over-abundance of α-SYN triggered the expression of NF-κB p65, and led to microglial activation and DA neurodegeneration; however, in mice deficient of gamma chain subunit of the Fc receptors (FcγR-/- mice), α-SYN-induced NF-κB signaling was blocked, while microglial activation …
C-C-Motif Chemokine Receptor/Ligand Gene Variants And Their Associations With Hiv-1 Transmission And Pathogenesis, Liangyuan Hu
C-C-Motif Chemokine Receptor/Ligand Gene Variants And Their Associations With Hiv-1 Transmission And Pathogenesis, Liangyuan Hu
All ETDs from UAB
Host factors including genes and their variants are important to HIV-1 acquisition, transmission and disease progression. In particular, chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have multiple variants of interest. We first investigated the impact of CCR2-CCR5 haplotypes on several outcomes among 567 HIV-1 discordant Zambian couples. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta=-0.58 log10 P=0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta=0.54, log10 P=0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by …
The Role Of Endoplasmic Reticulum Stress Response In Glioma Cell Death, G Johnson
The Role Of Endoplasmic Reticulum Stress Response In Glioma Cell Death, G Johnson
All ETDs from UAB
Malignant gliomas, including glioblastomas, are the main primary adult brain tumor. Even with current therapies, the median survival time for patients diagnosed with glioblastomas is only about 12 months. Therefore, it is imperative to identify pathways that can induce glioma cell death. This dissertation provides evidence defining how Endoplasmic Reticulum Stress Response (ERSR) induction promotes cell death selectively in malignant glioma cells (MGCs). I present data showing a correlation between ER Ca2+ storage abnormalities, ER ribosome-translocon expression and activity, ERSR intensity and cell death in MGCs. These data show ERSR induction with thapsigargin (THAP) results in a larger loss of …
A Study Of The Genetic Mechanisms Used To Regulate The Third Complementarity Determining Region Of The Immunoglobulin H Chain, Mohamed Khass
A Study Of The Genetic Mechanisms Used To Regulate The Third Complementarity Determining Region Of The Immunoglobulin H Chain, Mohamed Khass
All ETDs from UAB
Developing B cells exhibit sequential changes in the representation of immunoglobulin (Ig) heavy (H) chain sequences with excess hydrophobic or charged amino acids in complementarity determining region 3 (CDR-H3). To begin to elucidate the mechanisms by which this process occurs, we used Bromodeoxy Uridine (BrdU) incorporation and Annexin V binding to quantify B cell turnover and cell cycle progression in developing B cell subsets in the bone marrow, spleen and peritoneal cavity of wild-type BALB/c mice. To magnify the effects of hydrophobicity and charge, we included in this analysis mice limited to the use of an IgH allele with a …
Is P53 A Target Of Hpv-18 E6 In The Viral Life Cycle?, Eun-Young Kho
Is P53 A Target Of Hpv-18 E6 In The Viral Life Cycle?, Eun-Young Kho
All ETDs from UAB
The large family of human papillomaviruses (HPVs) infects the cutaneous or mucosal epithelia causing benign hyper proliferative diseases. Infections by the high-risk (HR) HPV genotypes in the anogenital tracts can progress to high grade lesions and cancers in men and women. Because the viral productive program requires squamous differentiation of epithelia, HPV encodes oncoproteins that recondition the differentiated cells that have withdrawn from the cell cycle to support viral DNA amplification. The HR HPV E6 and E7 oncogenes are selectively expressed in cervical carcinomas and are necessary to maintain the malignant state. In vitro, constitutive expression of the HR HPV …
Regulation Of Cell Death By Autophagy In Glial Neoplasms, Latika R. Kohli
Regulation Of Cell Death By Autophagy In Glial Neoplasms, Latika R. Kohli
All ETDs from UAB
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies of the peripheral nervous system. The majority of MPNSTs arise in patients of the autosomal dominant genetic disorder neurofibromatosis type I (NF1) although they also arise sporadically. In the absence of any effective chemotherapeutic options and with surgery constituting the mainstay of treatment, MPNST patients face an extremely poor prognosis. This underscores the need to develop novel therapeutic strategies against this tumor type. It is well accepted that the crosstalk between autophagy and apoptosis can be exploited to derive maximal therapeutic benefit, especially through combinatorial therapies. However, this interaction is extremely …
Mechanism Of Nfi-C Functionin During Tooth Root Formation, Ejvis Lamani
Mechanism Of Nfi-C Functionin During Tooth Root Formation, Ejvis Lamani
All ETDs from UAB
Currently, very little is known regarding tissue-specific gene regulation during the later stages of tooth development, especially those associated with root formation. Re-cent studies have identified nuclear factor I-C (NFI-C) as a critical factor for root for-mation in mammals. NFI-C functions as a cellular transcription factor and adenovirus DNA replication factor. Its role in root formation first became evident when Nfi-c null mice were shown to lack molar roots. A similar phenotype of incomplete or absent root formation is observed in patients with the autosomal dominant disease Radicular Dentin Dysplasia (RDD; MIM125400) also known as Rootless Teeth or Dentin Dysplasia …
Identification, Molecular Cloning And Characterization Of Transmitted/Founder Hiv-1 Subtype A, D And Ad Viruses And Envelope Glycoproteins, Joshua Baalwa
All ETDs from UAB
A precise molecular identification of transmitted/founder (T/F) HIV-1 genomes responsible for productive infection in humans can be an enabling strategy for elucidating mechanisms of virus transmission, immunopathogenesis and prevention. Previously, we reported a single genome sequencing approach, which when combined with a mathematical model of early random virus diversification, allowed for an unambiguous identification of T/F HIV-1 subtype B and C envelope (env) genes. Here, we apply this method to the identification and molecular cloning of full-length HIV-1 genomes and env genes of the less well-studied, but nonetheless important, HIV-1 subtypes A and D. Twelve subtype A (n=5), D (n=5) …
Structural Investigations Of Retinoid X Receptor Transcriptional Activation By Anti-Cancer Rexinoids, Leeann J. Boerma
Structural Investigations Of Retinoid X Receptor Transcriptional Activation By Anti-Cancer Rexinoids, Leeann J. Boerma
All ETDs from UAB
Nuclear receptor (NR) protein retinoid X receptor (RXR) is a ligand-inducible transcription factor that binds retinoids for regulation of target genes. Agonist binding induces a major structural rearrangement in the ligand binding domain (LBD) and formation of the coactivator binding interface. RXR-signaling pathways control proliferation, differentiation, and growth in epithelial tissues. To understand how RXR agonists enhance signaling at the molecular level requires an understanding of how agonists induce structural and dynamical changes in the LBD to recruit coactivators for activation of anti-cancer relevant transcription. While most studies of NR activation center on the position of Helix 12 (H12)/activation function-2 …
Serotonin Signaling In Angiogenesis, Ali Zamani
Serotonin Signaling In Angiogenesis, Ali Zamani
All ETDs from UAB
Serotonin (5-hydroxytryptamine, 5-HT) is a well-known "happy" neurotransmitter. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed class of antidepressant medications to raise the serotonin level in the brain. However, the majority of serotonin in the human body is present outside of the brain and stored in platelets in blood circulation. Blood coagulation is a common feature of malignant solid tumors and leads to significant serotonin release from activated platelets into tumor environment. Due to the unique feature of platelet in lacking nucleus, the impact of platelet and serotonin on cancer progression has been overlooked by studies focusing on cancer …
Neuropharmacology Of The Α2a Adrenergic Receptor In Disorders Of Mood And Cognition, Christopher Cottingham
Neuropharmacology Of The Α2a Adrenergic Receptor In Disorders Of Mood And Cognition, Christopher Cottingham
All ETDs from UAB
Depressive disorders carry relatively high lifetime risks of greater than 10%, and the antidepressant drugs used in the pharmacotherapy of these mood/cognitive disorders are among the most-prescribed pharmacological agents. However, a detailed understanding of both depressive etiology and the pharmacological mechanisms of action for antidepressant drugs remain elusive. The overall goal of this dissertation research is to provide novel in-sights through a detailed study of the neuropharmacology of the α2A adrenergic receptor (AR). α2ARs, as key regulators of noradrenergic neurotransmission, have been broadly understood to have some ill-defined role in both the neurobiology and neuropharmacology of depressive disorders. The studies …
Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva
Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva
All ETDs from UAB
Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus that causes a severe and often fatal disease in equids and humans. To date, despite a continuous public health threat, no vaccines or antiviral drugs against VEEV infection have been developed for human use. In this study we took advantage of accumulated knowledge of capsid protein function in viral replication, assembly and virus-host interactions. Besides being an integral part of the virion, capsid protein is the major determinant of VEEV pathogenesis. This protein is cytotoxic and induces cellular transcriptional shutoff as a countermeasure to the cellular antiviral response. We introduced targeted …
Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson
Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson
All ETDs from UAB
Pneumonia caused by the fungal pathogen Pneumocystis continues to be the leading cause of morbidity and mortality in AIDS patients. In addition, there are a number of other non-HIV-associated diseases that render an individual susceptible to Pneumocystis infection, including chronic obstructive pulmonary disease. Innate immune mechanisms are important for controlling Pneumocystis lung infection. As alveolar macrophages serve the front lines of lung host defense, our goal was to elucidate their responses during lung Pneumocystis infection. Here, we established a role for Src family kinases in the lung immune response to Pneumocystis, which uncovered a role for alternatively activated alveolar macrophages. …